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@article{faucris.242402796,
abstract = {Chromosomal 7q31 deletions have been described in individuals with variable neurodevelopmental phenotypes including speech and language impairment. These copy number variants usually encompass FOXP2, haploinsufficiency of which represents a widely acknowledged cause for specific speech and language disorders. By chromosomal microarray analysis we identified a 4.7 Mb microdeletion at 7q31.2q31.31 downstream of FOXP2 in three family members presenting with variable speech, language and neurodevelopmental phenotypes. The index individual showed delayed speech development with impaired speech production, reduced language comprehension, and additionally learning difficulties, microcephaly, and attention deficit. His younger sister had delayed speech development with impaired speech production and partially reduced language comprehension. Their mother had attended a school for children with speech and language deficiencies and presented with impaired articulation. The deletion had occurred de novo in the mother, includes 15 protein-coding genes and is located in close proximity to the 3′ end of FOXP2. Though a novel locus at 7q31.2q31.31 associated with mild neurodevelopmental and more prominent speech and language impairment is possible, the close phenotypic overlap with FOXP2-associated speech and language disorder rather suggests a positional effect on FOXP2 expression and function.},
author = {Rieger, Melissa and Krumbiegel, Mandy and Reuter, Miriam and Schützenberger, Anne and Reis, André and Zweier, Christiane},
doi = {10.1002/ajmg.a.61838},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
keywords = {7q; deletion; FOXP2; language; speech},
note = {CRIS-Team Scopus Importer:2020-09-11},
peerreviewed = {Yes},
title = {7q31.2q31.31 deletion downstream of {FOXP2} segregating in a family with speech and language disorder},
year = {2020}
}
@article{faucris.277574261,
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by aberrant alternative splicing (AS). Nuclear loss and cytoplasmic accumulation of the splicing factor TDP-43 in motor neurons (MN) are hallmarks of ALS at late stages of the disease. However, it is unknown if altered AS is present before TDP-43 pathology occurs. Here, we investigate altered AS and its origins in early stages of ALS using human induced pluripotent stem cell-derived motor neurons (MNs) from sporadic and familial ALS patients. We find high levels of the RNA-binding proteins NOVA1, NOVA2, and RBFOX2 in the insoluble protein fractions and observe that AS events in ALS-associated MNs are enriched for binding sites of these proteins. Our study points to an early disrupted function of NOVA1 that drives AS changes in a complex fashion, including events caused by a consistent loss of NOVA1 function. NOVA1 exhibits increased cytoplasmic protein levels in early stage MNs without TDP-43 pathology in ALS postmortem tissue. As nuclear TDP-43 protein level depletes, NOVA1 is reduced. Potential indications for a reduction of NOVA1 also came from mice over-expressing TDP-43 lacking its nuclear localization signal and iPSC-MN stressed with puromycin. This study highlights that additional RBP-RNA perturbations in ALS occur in parallel to TDP-43.},
author = {Krach, Florian and Wheeler, Emily C. and Regensburger, Martin and Börstler, Tom and Wend, Holger and Vu, Anthony Q. and Wang, Ruth and Reischl, Stephanie and Boldt, Karsten and Batra, Ranjan and Aigner, Stefan and Ravits, John and Winkler, Jürgen and Yeo, Gene W. and Winner, Beate},
doi = {10.1007/s00401-022-02450-3},
faupublication = {yes},
journal = {Acta Neuropathologica},
note = {CRIS-Team WoS Importer:2022-07-08},
peerreviewed = {Yes},
title = {{Aberrant} {NOVA1} function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis},
url = {https://link.springer.com/article/10.1007/s00401-022-02450-3#Ack1},
year = {2022}
}
@article{faucris.209650886,
abstract = {Biallelic variants in the AEBP1 gene cause a novel autosomal-recessive connective tissue disorder (CTD) reminiscent of Ehlers-Danlos Syndrome (EDS). The four previously reported individuals show considerable clinical variability. Unbiased high-throughput sequencing enables the rapid identification of additional cases for such rare entities. We identified the homozygous nonsense variant c.917dup, p.Tyr306* in AEBP1 using clinical exome sequencing in a female individual with previously unsolved CTD. Segregation testing confirmed homozygosity in the clinically affected brother and heterozygous carrier status in the healthy mother. Chromosomal microarray showed that the variant lies in a run of homozygosity, suggesting a common origin of this genomic segment. RT-PCR analysis in the mother revealed a monoallelic expression of the normal transcript supporting a nonsense-mediated mRNA decay and functional nullizygosity as disease mechanism. We describe two individuals from a fourth family with AEBP1-associated CTD. Our results further verify that autosomal-recessive inherited LOF variants in the AEBP1 gene cause clinical features of different EDS subtypes, but also of the marfanoid spectrum. As identification of further individuals is necessary to inform the clinical characterization, we stress the added value of exome sequencing for such rare diseases.},
author = {Hebebrand, Moritz and Vasileiou, Georgia and Krumbiegel, Mandy and Kraus, Cornelia and Uebe, Steffen and Ekici, Arif Bülent and Thiel, Christian and Reis, André and Popp, Bernt},
doi = {10.1002/ajmg.a.60679},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
note = {EVALuna2:35120},
peerreviewed = {Yes},
title = {{A} biallelic truncating {AEBP1} variant causes connective tissue disorder in two siblings},
year = {2018}
}
@inproceedings{faucris.248094052,
address = {LONDON},
author = {Hetzelt, Katalin and Kraus, Cornelia and Kusnik, Stefan and Thiel, C. and Ekici, Arif Bülent and Reis, André and Zweier, Christiane},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {867-867},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{A} case of autosomal recessive spinocerebellar ataxia type 18 with a novel mutation in {GRID2}},
year = {2020}
}
@article{faucris.240979406,
abstract = {Autosomal-recessive spinocerebellar ataxia type 18 (SCAR18) is a rare neurologic disorder. It is caused by bi-allelic aberrations in the GRID2 gene, encoding an ionotropic glutamate receptor. In total, 20 affected individuals with mainly homozygous/compound heterozygous intragenic deletions/duplications, two different missense variants and one nonsense variant in GRID2 have been reported, so far. SCAR18 is characterized by delayed psychomotor development, intellectual disability, severely impaired gait due to cerebellar ataxia, ocular movement abnormalities, and cerebellar atrophy in brain imaging. By trio exome sequencing, we now identified a novel homozygous nonsense variant (c.568C > T; p.Gln190*) in GRID2 in a four year old female from a consanguineous family who presented with a particularly severe manifestation of SCAR18. The girl was born after an uneventful pregnancy and showed early-onset, profoundly delayed psychomotor development with no achieved psychomotor milestones at age 4 years. Additionally, she presented with severe muscular hypotonia, progressive truncal and appendicular ataxia, binocular vertical nystagmus, central hearing loss and incomplete loss of sight. She was dystrophic, interacted only very little and had behavioral anomalies such as eating hair and bruxism. Brain imaging showed cerebellar hypoplasia, extended cerebrospinal fluid spaces and beginning reduction of cerebral volume. Our findings further delineate the mutational and clinical spectrum of GRID2-associated spinocerebellar ataxia type 18 and indicate that homozygous nonsense variants are possibly associated with the severe end of the SCAR18 phenotypic spectrum.},
author = {Hetzelt, Katalin and Kraus, Cornelia and Kusnik, Stefan and Thiel, Christian and Uebe, Steffen and Ekici, Arif Bülent and Trollmann, Regina and Reis, André and Zweier, Christiane},
doi = {10.1016/j.ejmg.2020.103998},
faupublication = {yes},
journal = {European Journal of Medical Genetics},
keywords = {Ataxia; Autosomal-recessive; Cerebellar hypoplasia; GRID2; Psychomotor development; SCAR18},
note = {CRIS-Team Scopus Importer:2020-07-31},
peerreviewed = {Yes},
title = {{A} case of severe autosomal recessive spinocerebellar ataxia type 18 with a novel nonsense variant in {GRID2}},
volume = {63},
year = {2020}
}
@article{faucris.122881484,
abstract = {In Parkinson's disease and dementia with Lewy bodies, ?-synuclein aggregates to form oligomers and fibrils; however, the precise nature of the toxic ?-synuclein species remains unclear. A number of synthetic ?-synuclein mutations were recently created (E57K and E35K) that produce species of ?-synuclein that preferentially form oligomers and increase ?-synuclein-mediated toxicity. We have shown that acute lentiviral expression of ?-synuclein E57K leads to the degeneration of dopaminergic neurons; however, the effects of chronic expression of oligomer-prone ?-synuclein in synapses throughout the brain have not been investigated. Such a study could provide insight into the possible mechanism(s) through which accumulation of ?-synuclein oligomers in the synapse leads to neurodegeneration. For this purpose, we compared the patterns of neurodegeneration and synaptic damage between a newly generated mThy-1 ?-synuclein E57K transgenic mouse model that is prone to forming oligomers and the mThy-1 ?-synuclein wild-type mouse model (Line 61), which accumulates various forms of ?-synuclein. Three lines of ?-synuclein E57K (Lines 9, 16 and 54) were generated and compared with the wild-type. The ?-synuclein E57K Lines 9 and 16 were higher expressings of ?-synuclein, similar to ?-synuclein wild-type Line 61, and Line 54 was a low expressing of ?-synuclein compared to Line 61. By immunoblot analysis, the higher-expressing ?-synuclein E57K transgenic mice showed abundant oligomeric, but not fibrillar, ?-synuclein whereas lower-expressing mice accumulated monomeric ?-synuclein. Monomers, oligomers, and fibrils were present in ?-synuclein wild-type Line 61. Immunohistochemical and ultrastructural analyses demonstrated that ?-synuclein accumulated in the synapses but not in the neuronal cells bodies, which was different from the ?-synuclein wild-type Line 61, which accumulates ?-synuclein in the soma. Compared to non-transgenic and lower-expressing mice, the higher-expressing ?-synuclein E57K mice displayed synaptic and dendritic loss, reduced levels of synapsin 1 and synaptic vesicles, and behavioural deficits. Similar alterations, but to a lesser extent, were seen in the ?-synuclein wild-type mice. Moreover, although the oligomer-prone ?-synuclein mice displayed neurodegeneration in the frontal cortex and hippocampus, the ?-synuclein wild-type only displayed neuronal loss in the hippocampus. These results support the hypothesis that accumulating oligomeric ?-synuclein may mediate early synaptic pathology in Parkinson's disease and dementia with Lewy bodies by disrupting synaptic vesicles. This oligomer-prone model might be useful for evaluating therapies directed at oligomer reduction.},
author = {Rockenstein, Edward and Nuber, Silke and Overk, Cassia R. and Ubhi, Kiren and Mante, Michael and Patrick, Christina and Adame, Anthony and Trejo-Morales, Margarita and Gerez, Juan and Picotti, Paola and Jensen, Poul H. and Campioni, Silvia and Riek, Roland and Winkler, Jürgen and Gage, Fred H. and Winner, Beate and Masliah, Eliezer},
doi = {10.1093/brain/awu057},
faupublication = {yes},
journal = {Brain},
note = {EVALuna2:25331},
pages = {1496-513},
peerreviewed = {Yes},
title = {{Accumulation} of oligomer-prone ?-synuclein exacerbates synaptic and neuronal degeneration in vivo},
volume = {137},
year = {2014}
}
@article{faucris.110874544,
abstract = {Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.},
author = {Aung, Tin and Ozaki, Mineo and Mizoguchi, Takanori and Allingham, R. Rand and Li, Zheng and Haripriya, Aravind and Nakano, Satoko and Uebe, Steffen and Harder, Jeffrey M. and Chan, Anita S. Y. and Lee, Mei Chin and Burdon, Kathryn P. and Astakhov, Yury S. and Abu-Amero, Khaled K. and Zenteno, Juan C. and Nilguen, Yildirim and Zarnowski, Tomasz and Pakravan, Mohammad and Abu Safieh, Leen and Jia, Liyun and Wang, Ya Xing and Williams, Susan and Paoli, Daniela and Schlottmann, Patricio G. and Huang, Lulin and Sim, Kar Seng and Foo, Jia Nee and Nakano, Masakazu and Ikeda, Yoko and Kumar, Rajesh S. and Ueno, Morio and Manabe, Shin-Ichi and Hayashi, Ken and Kazama, Shigeyasu and Ideta, Ryuichi and Mori, Yosai and Miyata, Kazunori and Sugiyama, Kazuhisa and Higashide, Tomomi and Chihara, Etsuo and Inoue, Kenji and Ishiko, Satoshi and Yoshida, Akitoshi and Yanagi, Masahide and Kiuchi, Yoshiaki and Aihara, Makoto and Ohashi, Tsutomu and Sakurai, Toshiya and Sugimoto, Takako and Chuman, Hideki and Matsuda, Fumihiko and Yamashiro, Kenji and Gotoh, Norimoto and Miyake, Masahiro and Astakhov, Sergei Y. and Osman, Essam A. and Al-Obeidan, Saleh A. and Owaidhah, Ohoud and Al-Jasim, Leyla and Al Shahwan, Sami and Fogarty, Rhys A. and Leo, Paul and Yetkin, Yaz and Oguz, Cilingir and Kanavi, Mozhgan Rezaei and Beni, Afsaneh Nederi and Yazdani, Shahin and Akopov, Evgeny L. and Toh, Kai-Yee and Howell, Gareth R. and Orr, Andrew C. and Goh, Yufen and Meah, Wee Yang and Peh, Su Qin and Kosior-Jarecka, Ewa and Lukasik, Urszula and Krumbiegel, Mandy and Vithana, Eranga N. and Wong, Tien Yin and Liu, Yutao and Koch, Allison E. Ashley and Challa, Pratap and Rautenbach, Robyn M. and Mackey, David A. and Hewitt, Alex W. and Mitchell, Paul and Wang, Jie Jin and Ziskind, Ari and Carmichael, Trevor and Ramakrishnan, Rangappa and Narendran, Kalpana and Venkatesh, Rangaraj and Vijayan, Saravanan and Zhao, Peiquan and Chen, Xueyi and Guadarrama-Vallejo, Dalia and Cheng, Ching Yu and Perera, Shamira A. and Husain, Rahat and Ho, Su-Ling and Welge-Lüssen, Ulrich-Christoph and Mardin, Christian Y. and Schlötzer-Schrehardt, Ursula and Hillmer, Axel M. and Herms, Stefan and Moebus, Susanne and Noethen, Markus M. and Weisschuh, Nicole and Shetty, Rohit and Ghosh, Arkasubhra and Teo, Yik Ying and Brown, Matthew A. and Lischinsky, Ignacio and Crowston, Jonathan G. and Coote, Michael and Zhao, Bowen and Sang, Jinghong and Zhang, Nihong and You, Qisheng and Vysochinskaya, Vera and Founti, Panayiota and Chatzikyriakidou, Anthoula and Lambropoulos, Alexandros and Anastasopoulos, Eleftherios and Coleman, Anne L. and Wilson, M. Roy and Rhee, Douglas J. and Kang, Jae Hee and May-Bolchakova, Inna and Heegaard, Steffen and Mori, Kazuhiko and Alward, Wallace L. M. and Jonas, Jost B. and Xu, Liang and Liebmann, Jeffrey M. and Chowbay, Balram and Schaeffeler, Elke and Schwab, Matthias and Lerner, Fabian and Wang, Ningli and Yang, Zhenglin and Frezzotti, Paolo and Kinoshita, Shigeru and Fingert, John H. and Inatani, Masaru and Tashiro, Kei and Reis, André and Edward, Deepak P. and Pasquale, Louis R. and Kubota, Toshiaki and Wiggs, Janey L. and Pasutto, Francesca and Topouzis, Fotis and Dubina, Michael and Craig, Jamie E. and Yoshimura, Nagahisa and Sundaresan, Periasamy and John, Simon W. M. and Ritch, Robert and Hauser, Michael A. and Khor, Chiea-Chuen},
doi = {10.1038/ng.3226},
faupublication = {yes},
journal = {Nature Genetics},
note = {EVALuna2:9286},
pages = {387-92},
peerreviewed = {Yes},
title = {{A} common variant mapping to {CACNA1A} is associated with susceptibility to exfoliation syndrome},
volume = {47},
year = {2015}
}
@article{faucris.107515804,
abstract = {We report on a consanguineous Pakistani family with a severe congenital microcephaly syndrome resembling the Seckel syndrome and Jawad syndrome. The affected individuals in this family were born to consanguineous parents of whom the mother presented with mild intellectual disability (ID), epilepsy and diabetes mellitus. The two living affected brothers presented with microcephaly, white matter disease of the brain, hyponychia, dysmorphic facial features with synophrys, epilepsy, diabetes mellitus and ID. Genotyping with a 250K SNP array in both affected brothers revealed an 18 MB homozygous region on chromosome 18 p11.21-q12.1 encompassing the SCKL2 locus of the Seckel and Jawad syndromes. Sequencing of the RBBP8 gene, underlying the Seckel and Jawad syndromes, identified the novel mutation c.919A>G, p.Arg307Gly, segregating in a recessive manner in the family. In addition, in the two affected brothers and their mother we have also found a heterozygous 607kb deletion, encompassing exons 13-19 of NRXN1. Bidirectional sequencing of the coding exons of NRXN1 did not reveal any other mutation on the other allele. It thus appears that the phenotype of the mildly affected mother can be explained by the NRXN1 deletion, whereas the more severe and complex microcephalic phenotype of the two affected brothers is due to the simultaneous deletion in NRXN1 and the homozygous missense mutation affecting RBBP8.},
author = {Agha, Zehra and Iqbal, Zafar and Azam, Maleeha and Siddique, Maimoona and Willemsen, Marjolein H. and Kleefstra, Tjitske and Zweier, Christiane and De Leeuw, Nicole and Qamar, Raheel and Van Bokhoven, Hans},
doi = {10.1016/j.gene.2014.01.027},
faupublication = {yes},
journal = {Gene},
note = {EVALuna2:9226},
pages = {30-5},
peerreviewed = {Yes},
title = {{A} complex microcephaly syndrome in a {Pakistani} family associated with a novel missense mutation in {RBBP8} and a heterozygous deletion in {NRXN1}},
volume = {538},
year = {2014}
}
@article{faucris.111737384,
abstract = {The p.Thr124Met mutation in the myelin protein zero (MPZ) causes the Charcot-Marie-Tooth disease type 2J, a peripheral neuropathy with additional symptoms as pupillary alterations and deafness. It was observed in several families around the world originating e. g. from Germany, Belgium, Japan, Italy and North America. Here we report Central American patients originating from a family in Costa Rica carrying this mutation. Clinical, electrophysiological and molecular analysis of patients and controls were performed, including gene and linked markers' sequencing. Carriers share almost the entire haplotype with two non related Belgian CMT patients. As a result of the haplotype analysis, based on ten markers (seven SNPs, two microsatellites and an intronic polyA stretch), the founder effect hypothesis for this allele migration is suggestive.},
author = {Leal, Alejandro and Berghoff, Corinna and Berghoff, Martin and Rojas-Araya, Melissa and Ortiz, Carolina and Heuss, Dieter and Del Valle, Gerardo and Rautenstrauß, Bernd},
faupublication = {yes},
journal = {Revista De Biologia Tropical},
note = {EVALuna2:22390},
pages = {1285-93},
peerreviewed = {Yes},
title = {{A} {Costa} {Rican} family affected with {Charcot}-{Marie}-{Tooth} disease due to the myelin protein zero ({MPZ}) p.{Thr124Met} mutation shares the {Belgian} haplotype},
volume = {62},
year = {2014}
}
@article{faucris.274880240,
abstract = {We investigated the roles of interleukin 28A (also called IL28A or interferon λ2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing.\n and Stat1IEC-KO mice also developed more severe colitis in response to oxazolone than control mice. We found IL28 to induce phosphorylation (activation) of STAT1 in epithelial cells, leading to their proliferation in organoid culture. Administration of IL28 to mice with induced colonic wounds promoted mucosal healing.\n). We used high-resolution mini-endoscopy and in vivo imaging methods to assess colitis progression. We used 3-dimensional small intestine and colon organoids, along with RNA-Seq and gene ontology methods, to characterize the effects of IL28 on primary IECs. We studied the effects of IL28 on the human intestinal cancer cell line Caco-2 in a wound-healing assay, and in mice colon wounds. Colonic biopsies and resected tissue from patients with IBD (n = 62) and patients without colon inflammation (controls, n = 23) were analyzed by quantitative polymerase chain rection to measure expression of IL28A, IL28RA, and other related cytokines; biopsy samples were also analyzed by immunofluorescence to identify sources of IL28 production. IECs were isolated from patient tissues and incubated with IL28; signal transducer and activator of transcription 1 (STAT1) phosphorylation was measured by immunoblots and confocal imaging.\nIL28 controls proliferation of IECs in mice with colitis and accelerates mucosal healing by activating STAT1. IL28 might be developed as a therapeutic agent for patients with IBD.\nBACKGROUND & AIMS\nRESULTS\nMETHODS\nCONCLUSIONS},
author = {Chiriac, Mircea-Teodor and Buchen, Barbara and Wandersee, Alexandra and Hundorfean, Gheorghe and Günther, Claudia and Bourjau, Yvonne and Doyle, Sean E. and Frey, Benjamin and Ekici, Arif Bülent and Büttner, Christian and Weigmann, Benno and Atreya, Raja and Wirtz, Stefan and Becker, Christoph and Siebler, Jürgen and Neurath, Markus},
doi = {10.1053/j.gastro.2017.03.015},
faupublication = {yes},
journal = {Gastroenterology},
keywords = {Crohn’s Disease; Interferon λ; Ulcerative Colitis; Wound Healing},
pages = {123-138.e8},
peerreviewed = {Yes},
title = {{Activation} of {Epithelial} {Signal} {Transducer} and {Activator} of {Transcription} 1 by {Interleukin} 28 {Controls} {Mucosal} {Healing} in {Mice} {With} {Colitis} and {Is} {Increased} in {Mucosa} of {Patients} {With} {Inflammatory} {Bowel} {Disease}.},
volume = {153},
year = {2017}
}
@article{faucris.122797884,
abstract = {We investigated the roles of interleukin 28A (also called IL28A or interferon ?2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing.Colitis was induced in C57BL/6JCrl mice (controls), mice with IEC-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon ? receptor 1 gene (Il28ra(-/-)), and mice with disruption of the interferon regulatory factor 3 gene (Irf3(-/-)), with or without disruption of Irf7 (Irf7(-/-)). We used high-resolution mini-endoscopy and in vivo imaging methods to assess colitis progression. We used 3-dimensional small intestine and colon organoids, along with RNA-Seq and gene ontology methods, to characterize the effects of IL28 on primary IECs. We studied the effects of IL28 on the human intestinal cancer cell line Caco-2 in a wound-healing assay, and in mice colon wounds. Colonic biopsies and resected tissue from patients with IBD (n = 62) and patients without colon inflammation (controls, n = 23) were analyzed by quantitative polymerase chain rection to measure expression of IL28A, IL28RA, and other related cytokines; biopsy samples were also analyzed by immunofluorescence to identify sources of IL28 production. IECs were isolated from patient tissues and incubated with IL28; signal transducer and activator of transcription 1 (STAT1) phosphorylation was measured by immunoblots and confocal imaging.Lamina propria cells in colon tissues of patients with IBD, and mice with colitis, had increased expression of IL28 compared with controls; levels of IL28R were increased in the colonic epithelium of patients with IBD and mice with colitis. Administration of IL28 induced phosphorylation of STAT1 in primary human and mouse IECs, increasing with dose. Il28ra(-/-), Irf3(-/-), Irf3(-/-)Irf7(-/-), as well as Stat1IEC-KO mice, developed more severe colitis after administration of dextran sulfate sodium than control mice, with reduced epithelial restitution. Il28ra(-/-) and Stat1IEC-KO mice also developed more severe colitis in response to oxazolone than control mice. We found IL28 to induce phosphorylation (activation) of STAT1 in epithelial cells, leading to their proliferation in organoid culture. Administration of IL28 to mice with induced colonic wounds promoted mucosal healing.IL28 controls proliferation of IECs in mice with colitis and accelerates mucosal healing by activating STAT1. IL28 might be developed as a therapeutic agent for patients with IBD.},
author = {Chiriac, Mircea T. and Buchen, Barbara and Wandersee, Alexandra and Hundorfean, Gheorghe and Günther, Claudia and Bourjau, Yvonne and Doyle, Sean E. and Frey, Benjamin and Ekici, Arif Bülent and Büttner, Christian and Weigmann, Benno and Atreya, Raja and Wirtz, Stefan and Becker, Christoph and Neurath, Markus and Siebler, Jürgen},
doi = {10.1053/j.gastro.2017.03.015},
faupublication = {yes},
journal = {Gastroenterology},
note = {EVALuna2:9356},
pages = {123-138.e8},
peerreviewed = {Yes},
title = {{Activation} of {Epithelial} {Signal} {Transducer} and {Activator} of {Transcription} 1 by {Interleukin} 28 {Controls} {Mucosal} {Healing} in {Mice} {With} {Colitis} and {Is} {Increased} in {Mucosa} of {Patients} {With} {Inflammatory} {Bowel} {Disease}},
volume = {153},
year = {2017}
}
@article{faucris.274880803,
abstract = {We investigated the roles of interleukin 28A (also called IL28A or interferon λ2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing.\n and Stat1IEC-KO mice also developed more severe colitis in response to oxazolone than control mice. We found IL28 to induce phosphorylation (activation) of STAT1 in epithelial cells, leading to their proliferation in organoid culture. Administration of IL28 to mice with induced colonic wounds promoted mucosal healing.\n). We used high-resolution mini-endoscopy and in vivo imaging methods to assess colitis progression. We used 3-dimensional small intestine and colon organoids, along with RNA-Seq and gene ontology methods, to characterize the effects of IL28 on primary IECs. We studied the effects of IL28 on the human intestinal cancer cell line Caco-2 in a wound-healing assay, and in mice colon wounds. Colonic biopsies and resected tissue from patients with IBD (n = 62) and patients without colon inflammation (controls, n = 23) were analyzed by quantitative polymerase chain rection to measure expression of IL28A, IL28RA, and other related cytokines; biopsy samples were also analyzed by immunofluorescence to identify sources of IL28 production. IECs were isolated from patient tissues and incubated with IL28; signal transducer and activator of transcription 1 (STAT1) phosphorylation was measured by immunoblots and confocal imaging.\nIL28 controls proliferation of IECs in mice with colitis and accelerates mucosal healing by activating STAT1. IL28 might be developed as a therapeutic agent for patients with IBD.\nBACKGROUND & AIMS\nRESULTS\nMETHODS\nCONCLUSIONS},
author = {Chiriac, Mircea-Teodor and Buchen, Barbara and Wandersee, Alexandra and Hundorfean, Gheorghe and Günther, Claudia and Bourjau, Yvonne and Doyle, Sean E. and Frey, Benjamin and Ekici, Arif Bülent and Büttner, Christian and Weigmann, Benno and Atreya, Raja and Wirtz, Stefan and Becker, Christoph and Siebler, Jürgen and Neurath, Markus},
doi = {10.1053/j.gastro.2017.03.015},
faupublication = {yes},
journal = {Gastroenterology},
keywords = {Crohn’s Disease; Interferon λ; Ulcerative Colitis; Wound Healing},
pages = {123-138.e8},
peerreviewed = {Yes},
title = {{Activation} of {Epithelial} {Signal} {Transducer} and {Activator} of {Transcription} 1 by {Interleukin} 28 {Controls} {Mucosal} {Healing} in {Mice} {With} {Colitis} and {Is} {Increased} in {Mucosa} of {Patients} {With} {Inflammatory} {Bowel} {Disease}},
volume = {153},
year = {2017}
}
@article{faucris.273559530,
abstract = {Background and purpose: Atrial fibrillation (AF) in stroke patients can be classified as either “known AF” (KAF), defined as AF confirmed before stroke onset, or “AF detected after stroke” (AFDAS), defined as AF diagnosed after stroke onset. While KAF is considered primarily cardiogenic, AFDAS includes patients with stroke-triggered neurogenic arrhythmias. This study aimed to investigate the clinical course of stroke, functional outcomes and the value of oral anticoagulation (OAC) for secondary prevention according to AF subtype. Methods: Acute ischemic stroke patients were consecutively enrolled and AF was classified as AFDAS or KAF. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and 3-month functional outcomes were measured on the modified Rankin scale. Inverse probability weighting was applied to adjust for baseline confounders in patients with AFDAS and KAF. Multivariate logistic regression models were calculated to investigate the value of OAC for secondary prevention. Results: A total of 822 stroke patients with AF were included, of whom 234 patients (28.5%) had AFDAS. AFDAS patients had a lower prevalence of coronary artery disease, heart failure, and sustained AF, but higher rates of large vessel occlusion compared to KAF patients. NIHSS scores were lower in patients on pre-stroke anticoagulation. OAC for secondary prevention was associated with favorable 3-month functional outcome (odds ratio 7.60, 95% confidence interval 3.42–16.88) independently of AF subtype. The rate of stroke recurrence did not differ significantly. Conclusions: Clinical characteristics suggest that AFDAS might comprise a distinct pathophysiological and clinical entity among stroke patients with AF. The benefit of anticoagulation for secondary prevention was not affected by AF subtype.},
author = {Wang, Ruihao and Macha, Kosmas and Haupenthal, David and Gaßmann, Luise and Siedler, Gabriela and Stoll, Svenja and Fröhlich, Kilian and Köhn, Julia and Schwab, Stefan and Kallmünzer, Bernd},
doi = {10.1111/ene.15338},
faupublication = {yes},
journal = {European Journal of Neurology},
keywords = {acute ischemic stroke; atrial fibrillation detected after stroke; known atrial fibrillation; modified Rankin scale; oral anticoagulation; stroke recurrence},
note = {CRIS-Team Scopus Importer:2022-04-22},
peerreviewed = {Yes},
title = {{Acute} care and secondary prevention of stroke with newly detected versus known atrial fibrillation},
year = {2022}
}
@article{faucris.208410575,
abstract = {BACKGROUND: Breast cancer is the most common cancer in women. 12-15% of all tumors are triple-negative breast cancers (TNBC). So far, TNBC has been mainly associated with mutations in BRCA1. The presence of other predisposing genes seems likely since DNA damage repair is a complex process that involves several genes. Therefore we investigated if mutations in other genes are involved in cancer development and whether TNBC is an additional indicator of mutational status besides family history and age of onset.
METHODS: We performed a germline panel-based screening of 10 high and low-moderate penetrance breast cancer susceptibility genes (BRCA1, BRCA2, ATM, CDH1, CHEK2, NBN, PALB2, RAD51C, RAD51D and TP53) in 229 consecutive individuals affected with TNBC unselected for age, family history or bilateral disease. Within this cohort we compared the number of mutation carriers fulfilling clinical selection criteria with the total number of carriers identified.
RESULTS: Age at diagnosis ranged from 23 to 80 years with an average age of 50.2 years. In 57 women (24.9%) we detected a pathogenic mutation, with a higher frequency (29.7%) in the group manifesting cancer before 60 years. Deleterious BRCA1 mutations occurred in 14.8% of TNBC patients. These were predominantly recurrent frameshift mutations (24/34, 70.6%). Deleterious BRCA2 mutations occurred in 5.7% of patients, all but one (c.1813dupA) being unique. While no mutations were found in CDH1 and TP53, 10 mutations were detected in one of the six other predisposition genes. Remarkably, neither of the ATM, RAD51D, CHEK2 and PALB2 mutation carriers had a family history. Furthermore, patients with non-BRCA1/2 mutations were not significantly younger than mutation negative women (p = 0.3341). Most importantly, among the 57 mutation carriers, ten (17.5%) would be missed using current clinical testing criteria including five (8%) with BRCA1/2 mutations.
CONCLUSIONS: In summary, our data confirm and expand previous studies of a high frequency of germline mutations in genes associated with ineffective repair of DNA damage in women with TNBCs. Neither age of onset, contralateral disease nor family history were able to discern all mutation positive individuals. Therefore, TNBC should be considered as an additional criterion for panel based genetic testing.},
author = {Hoyer, Juliane and Vasileiou, Georgia and Uebe, Steffen and Wunderle, Marius and Kraus, Cornelia and Fasching, Peter and Thiel, Christian and Hartmann, Arndt and Beckmann, Matthias and Lux, Michael P. and Reis, André},
doi = {10.1186/s12885-018-4821-8},
faupublication = {yes},
journal = {BMC Cancer},
note = {EVALuna2:34811},
peerreviewed = {Yes},
title = {{Addition} of triple negativity of breast cancer as an indicator for germline mutations in predisposing genes increases sensitivity of clinical selection criteria},
volume = {18},
year = {2018}
}
@article{faucris.120816124,
abstract = {In Parkinson's disease (PD) and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research.},
author = {Regensburger, Martin and Prots, Iryna and Winner, Beate},
doi = {10.1155/2014/454696},
faupublication = {yes},
journal = {Neural Plasticity},
note = {EVALuna2:26222},
pages = {454696},
peerreviewed = {Yes},
title = {{Adult} hippocampal neurogenesis in {Parkinson}'s disease: impact on neuronal survival and plasticity},
volume = {2014},
year = {2014}
}
@article{faucris.274824171,
abstract = {The generation and maturation of adult neural stem/progenitor cells are impaired in many neurodegenerative diseases, among them is Parkinson's disease (PD). In mammals, including humans, adult neurogenesis is a lifelong feature of cellular brain plasticity in the hippocampal dentate gyrus (DG) and in the subventricular zone (SVZ)/olfactory bulb system. Hyposmia, depression, and anxiety are early non-motor symptoms in PD. There are parallels between brain regions associated with non-motor symptoms in PD and neurogenic regions. In autosomal dominant PD, mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are frequent LRRK2 homologs in non-vertebrate systems play an important role in chemotaxis, cell polarity, and neurite arborization. We investigated adult neurogenesis and the neurite development of new neurons in the DG and SVZ/olfactory bulb system in bacterial artificial chromosome (BAC) human Lrrk2 G2019S transgenic mice. We report that mutant human Lrrk2 is highly expressed in the hippocampus in the DG and the SVZ of adult Lrrk2 G2019S mice. Proliferation of newly generated cells is significantly decreased and survival of newly generated neurons in the DG and olfactory bulb is also severely impaired. In addition, after stereotactic injection of a GFP retrovirus, newly generated neurons in the DG of Lrrk2 G2019S mice exhibited reduced dendritic arborization and fewer spines. This loss in mature, developed spines might point towards a decrease in synaptic connectivity. Interestingly, physical activity partially reverses the decrease in neuroblasts observed in Lrrk2 G2010S mice. These data further support a role for Lrrk2 in neuronal morphogenesis and provide new insights into the role of Lrrk2 in adult neurogenesis. Published by Elsevier Inc.},
author = {Winner, Beate and Gage, Fred H. and Winkler, Jürgen and et al.},
author_hint = {Winner B, Melrose HL, Zhao C, Hinkle KM, Yue M, Kent C, Braithwaite AT, Ogholikhan S, Aigner R, Winkler J, Farrer MJ, Gage FH},
doi = {10.1016/j.nbd.2010.12.008},
faupublication = {no},
journal = {Neurobiology of Disease},
keywords = {Neural progenitor cells;Neurogenesis;Parkinson's disease;Dendrites;Spines;LRRK2},
pages = {706-716},
peerreviewed = {Yes},
support_note = {Author relations incomplete. You may find additional data in field 'author{\_}hint'},
title = {{Adult} neurogenesis and neurite outgrowth are impaired in {LRRK2} {G2019S} mice},
volume = {41},
year = {2011}
}
@article{faucris.120611084,
abstract = {Adult neurogenesis is limited to specific brain regions in the mammalian brain, such as the hippocampal dentate gyrus and the subventricular zone/olfactory bulb system. Alterations in adult neurogenesis appear to be a common hallmark in different neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). This is remarkable, because the distinct pathological proteins responsible for the different diseases induce the loss of different neural populations. Impaired adult neurogenesis was shown in numerous animal models of neurodegenerative diseases; however, only few postmortem studies have been performed. We will review concepts related to the interplay between cellular plasticity in regions of adult neurogenesis with a specific focus on cell-autonomous and non-cell-autonomous factors. Furthermore, various strategies aimed to stimulate neuronal plasticity will be discussed within the context of a potential translation into therapeutic approaches for neuropsychiatric symptoms associated with PD, HD, and AD.},
author = {Winner, Beate and Winkler, Jürgen},
doi = {10.1101/cshperspect.a021287},
faupublication = {yes},
journal = {Cold Spring Harbor Perspectives in Biology},
note = {EVALuna2:25348},
pages = {a021287},
peerreviewed = {Yes},
title = {{Adult} neurogenesis in neurodegenerative diseases},
volume = {7},
year = {2015}
}
@article{faucris.289021978,
abstract = {Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes’ coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10−6) and AC058822.1 (P = 1.47 × 10−4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10−5), demonstrating the importance of diversifying study cohorts.},
author = {Mueller, Stefanie H. and Lai, Alvina G. and Valkovskaya, Maria and Michailidou, Kyriaki and Bolla, Manjeet K. and Wang, Qin and Dennis, Joe and Lush, Michael and Abu-Ful, Zomoruda and Ahearn, Thomas U. and Andrulis, Irene L. and Anton-Culver, Hoda and Antonenkova, Natalia N. and Arndt, Volker and Aronson, Kristan J. and Augustinsson, Annelie and Baert, Thais and Freeman, Laura E.Beane and Beckmann, Matthias and Behrens, Sabine and Benitez, Javier and Bermisheva, Marina and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Stig E. and Bonanni, Bernardo and Brenner, Hermann and Brucker, Sara Y. and Buys, Saundra S. and Castelao, Jose E. and Chan, Tsun L. and Chang-Claude, Jenny and Chanock, Stephen J. and Choi, Ji Yeob and Chung, Wendy K. and Sahlberg, Kristine K. and Børresen-Dale, Anne Lise and Ottestad, Lars and Kåresen, Rolf and Schlichting, Ellen and Holmen, Marit Muri and Sauer, Toril and Haakensen, Vilde and Engebråten, Olav and Naume, Bjørn and Fosså, Alexander and Kiserud, Cecile E. and Reinertsen, Kristin V. and Helland, Åslaug and Riis, Margit and Geisler, Jürgen and Grenaker Alnaes, Grethe I. and Colonna, Sarah V. and Cornelissen, Sten and Couch, Fergus J. and Czene, Kamila and Daly, Mary B. and Devilee, Peter and Dörk, Thilo and Dossus, Laure and Dwek, Miriam and Eccles, Diana M. and Ekici, Arif Bülent and Eliassen, A. Heather and Engel, Christoph and Evans, D. Gareth and Fasching, Peter and Fletcher, Olivia and Flyger, Henrik and Gago-Dominguez, Manuela and Gao, Yu Tang and García-Closas, Montserrat and García-Sáenz, José A. and Genkinger, Jeanine and Gentry-Maharaj, Aleksandra and Grassmann, Felix and Guénel, Pascal and Gündert, Melanie and Häberle, Lothar and Hahnen, Eric and Haiman, Christopher A. and Håkansson, Niclas and Hall, Per and Harkness, Elaine F. and Harrington, Patricia A. and Hartikainen, Jaana M. and Hartman, Mikael and Hein, Alexander and Ho, Weang Kee and Hooning, Maartje J. and Hoppe, Reiner and Hopper, John L. and Houlston, Richard S. and Howell, Anthony and Hunter, David J. and Huo, Dezheng and Marsh, Deborah and Scott, Rodney and Baxter, Robert and Yip, Desmond and Carpenter, Jane and Davis, Alison and Pathmanathan, Nirmala and Simpson, Peter and Graham, Dinny and Sachchithananthan, Mythily and Ito, Hidemi and Iwasaki, Motoki and Jakubowska, Anna and Janni, Wolfgang and John, Esther M. and Jones, Michael E. and Jung, Audrey and Kaaks, Rudolf and Kang, Daehee and Khusnutdinova, Elza K. and Kim, Sung Won and Kitahara, Cari M. and Koutros, Stella and Kraft, Peter and Kristensen, Vessela N. and Kubelka-Sabit, Katerina and Kurian, Allison W. and Kwong, Ava and Lacey, James V. and Lambrechts, Diether and Le Marchand, Loic and Li, Jingmei and Linet, Martha and Lo, Wing Yee and Long, Jirong and Lophatananon, Artitaya and Mannermaa, Arto and Manoochehri, Mehdi and Margolin, Sara and Matsuo, Keitaro and Mavroudis, Dimitrios and Menon, Usha and Muir, Kenneth and Murphy, Rachel A. and Nevanlinna, Heli and Newman, William G. and Niederacher, Dieter and O’Brien, Katie M. and Obi, Nadia and Offit, Kenneth and Olopade, Olufunmilayo I. and Olshan, Andrew F. and Olsson, Håkan and Park, Sue K. and Patel, Alpa V. and Patel, Achal and Perou, Charles M. and Peto, Julian and Pharoah, Paul D.P. and Plaseska-Karanfilska, Dijana and Presneau, Nadege and Rack, Brigitte and Radice, Paolo and Ramachandran, Dhanya and Rashid, Muhammad U. and Rennert, Gad and Romero, Atocha and Ruddy, Kathryn J. and Rübner, Matthias and Saloustros, Emmanouil and Sandler, Dale P. and Sawyer, Elinor J. and Schmidt, Marjanka K. and Schmutzler, Rita K. and Schneider, Michael and Scott, Christopher and Shah, Mitul and Sharma, Priyanka and Shen, Chen Yang and Shu, Xiao Ou and Simard, Jacques and Surowy, Harald and Tamimi, Rulla M. and Tapper, William J. and Taylor, Jack A. and Teo, Soo Hwang and Teras, Lauren R. and Toland, Amanda E. and Tollenaar, Rob A.E.M. and Torres, Diana and Torres-Mejía, Gabriela and Troester, Melissa A. and Truong, Thérèse and Vachon, Celine M. and Vijai, Joseph and Weinberg, Clarice R. and Wendt, Camilla and Winqvist, Robert and Wolk, Alicja and Wu, Anna H. and Yamaji, Taiki and Yang, Xiaohong R. and Yu, Jyh Cherng and Zheng, Wei and Ziogas, Argyrios and Ziv, Elad and Dunning, Alison M. and Easton, Douglas F. and Hemingway, Harry and Hamann, Ute and Kuchenbaecker, Karoline B.},
doi = {10.1186/s13073-022-01152-5},
faupublication = {yes},
journal = {Genome Medicine},
keywords = {Breast cancer susceptibility; Diverse ancestry; Gene regulation; Genome-wide association study; Rare variants},
note = {CRIS-Team Scopus Importer:2023-02-10},
peerreviewed = {Yes},
title = {{Aggregation} tests identify new gene associations with breast cancer in populations with diverse ancestry},
volume = {15},
year = {2023}
}
@article{faucris.110850124,
abstract = {Intellectual disability is a highly heterogeneous disease that affects the central nervous system and impairs patients' ability to function independently. Despite multiples genes involved in the etiology of disease, most of the genetic background is yet to be discovered. We used runs of homozygosity and exome sequencing to study a large Costa Rican family with four individuals affected with severe intellectual disability and found a novel homozygous missense mutation, p. 96G>R, c. 286G>A, in all affected individuals. This gene encodes for a pyridoxal enzyme involved in the production of the neurotransmitter glutamate and is highly expressed in the white matter of brain and cerebellum. Protein modeling of GPT2 predicted that the mutation is located in a loop where the substrate binds to the active site of the enzyme, therefore, suggesting that the catalytic activity is impaired. With our report of a second mutation we fortify the importance of GPT2 as a novel cause of autosomal recessive nonsyndromic intellectual disability and support the premise that GPT2 is highly important for the neurodevelopment of the central nervous system.The mutation p. 96G>R c. 286G>A in GPT2, located in a loop where the substrate binds to the active site of the enzyme, fortifies the importance of GPT2 in the pathogenesis of nonsyndromic intellectual disability.},
author = {Lobo-Prada, Tanya and Sticht, Heinrich and Bogantes-Ledezma, Sixto and Ekici, Arif Bülent and Uebe, Steffen and Reis, André and Leal, Alejandro},
doi = {10.1007/8904{\_}2016{\_}40},
faupublication = {yes},
journal = {JIMD reports},
note = {EVALuna2:9390},
pages = {59-66},
peerreviewed = {Yes},
title = {{A} {Homozygous} {Mutation} in {GPT2} {Associated} with {Nonsyndromic} {Intellectual} {Disability} in a {Consanguineous} {Family} from {Costa} {Rica}},
volume = {36},
year = {2017}
}
@article{faucris.252893179,
abstract = {Oxidative stress (OS), mitochondrial dysfunction, and dysregulation of alpha-synuclein (aSyn) homeostasis are key pathogenic factors in Parkinson's disease. Nevertheless, the role of aSyn in mitochondrial physiology remains elusive. Thus, we addressed the impact of aSyn specifically on mitochondrial response to OS in neural cells. We characterize a distinct type of mitochondrial fragmentation, following H2O2 or 6-OHDA-induced OS, defined by spherically-shaped and hyperpolarized mitochondria, termed "mitospheres". Mitosphere formation mechanistically depended on the fission factor Drp1, and was paralleled by reduced mitochondrial fusion. Furthermore, mitospheres were linked to a decrease in mitochondrial activity, and preceded Caspase3 activation. Even though fragmentation of dysfunctional mitochondria is considered to be a prerequisite for mitochondrial degradation, mitospheres were not degraded via Parkin-mediated mitophagy. Importantly, we provide compelling evidence that aSyn prevents mitosphere formation and reduces apoptosis under OS. In contrast, aSyn did not protect against Rotenone, which led to a different, previously described donut-shaped mitochondrial morphology. Our findings reveal a dichotomic role of aSyn in mitochondrial biology, which is linked to distinct types of stress-induced mitochondrial fragmentation. Specifically, aSyn may be part of a cellular defense mechanism preserving neural mitochondrial homeostasis in the presence of increased OS levels, while not protecting against stressors directly affecting mitochondrial function.},
author = {Winner, Beate and Menges, Stefanie and Minakaki, Georgia and Schaefer, Patrick and Meixner, Holger and Prots, Iryna and Schlötzer-Schrehardt, Ursula and Friedland, Kristina and Outeiro, Tiago F. and Winklhofer, Konstanze F. and Von Arnim, Christine A. F. and Xiang, Wei and Winkler, Jürgen and Klucken, Jochen},
doi = {10.1038/srep42942},
faupublication = {yes},
journal = {Scientific Reports},
pages = {42942},
peerreviewed = {Yes},
title = {{Alpha}-synuclein prevents the formation of spherical mitochondria and apoptosis under oxidative stress},
volume = {7},
year = {2017}
}
@article{faucris.280365611,
abstract = {Background The prevalence of end-stage renal disease of unknown etiology in adult patients is globally high and accounts for almost 20% of all dialysis patients. Recent studies have suggested that the percentage of adult patients with a causal genetic variant has been underestimated so far. Despite severe prognostic and therapeutic implications, awareness about prevalence and manifestations of genetic kidney diseases in adult renal patients is still limited. Methods We recruited 58 individuals from 39 families at our transplantation center, fulfilling at least one of the following criteria: (i) unclear etiology of kidney disease, (ii) clinically suspected genetic kidney disease and (iii) positive family history for nephropathies. The cohort consisted of patients waitlisted for kidney transplantation and patients in the follow-up after transplantation. Detailed documentation of family history and phenotype was obtained before initiating gene panel sequencing of 479 nephropathy-associated genes. Results With this study design, a molecular genetic diagnosis was established in one-third of all patients. Mutations in the collagen COL4A genes, and mutations in MUC1 and UMOD were the most frequent among all detected causal variants. Overall, rare genetic variants were detected in more than half of all cases. Conclusion The combination of detailed phenotyping prior to next-generation sequencing diagnostics was highly efficient. Elucidating the underlying genetic causes in a cohort of adult renal patients has considerable clinical impact on medical management.},
author = {Leenen, Esther and Erger, Florian and Altmuller, Janine and Wenzel, Andrea and Thiele, Holger and Harth, Ana and Tschernoster, Nikolai and Lokhande, Shanti and Joerres, Achim and Becker, Jan-Ulrich and Ekici, Arif Bülent and Huettel, Bruno and Beck, Bodo and Weidemann, Alexander},
doi = {10.1093/ndt/gfac163},
faupublication = {yes},
journal = {Nephrology Dialysis Transplantation},
note = {CRIS-Team WoS Importer:2022-08-12},
peerreviewed = {Yes},
title = {{Alport} syndrome and autosomal dominant tubulointerstitial kidney disease frequently underlie end-stage renal disease of unknown origin-a single-center analysis},
year = {2022}
}
@article{faucris.298875053,
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a complex and incurable neurodegenerative disorder in which genetic and epigenetic factors contribute to the pathogenesis of all forms of ALS. The interplay of genetic predisposition and environmental footprints generates epigenetic signatures in the cells of affected tissues, which then alter transcriptional programs. Epigenetic modifications that arise from genetic predisposition and systemic environmental footprints should in theory be detectable not only in affected CNS tissue but also in the periphery. Here, we identify an ALS-associated epigenetic signature (‘epiChromALS’) by chromatin accessibility analysis of blood cells of ALS patients. In contrast to the blood transcriptome signature, epiChromALS includes also genes that are not expressed in blood cells; it is enriched in CNS neuronal pathways and it is present in the ALS motor cortex. By combining simultaneous ATAC-seq and RNA-seq with single-cell sequencing in PBMCs and motor cortex from ALS patients, we demonstrate that epigenetic changes associated with the neurodegenerative disease can be found in the periphery, thus strongly suggesting a mechanistic link between the epigenetic regulation and disease pathogenesis.},
author = {Kühlwein, Julia K. and Ruf, Wolfgang P. and Kandler, Katharina and Witzel, Simon and Lang, Christina and Mulaw, Medhanie A. and Ekici, Arif Bülent and Weishaupt, Jochen H. and Ludolph, Albert C. and Grozdanov, Veselin and Danzer, Karin M.},
doi = {10.1007/s00018-023-04769-w},
faupublication = {yes},
journal = {Cellular and Molecular Life Sciences},
keywords = {Chromatin remodeling; Epigenome; Integrated analysis; Motor neuron disease; Regulatory elements; Single-nuclei sequencing},
note = {CRIS-Team Scopus Importer:2023-05-05},
peerreviewed = {Yes},
title = {{ALS} is imprinted in the chromatin accessibility of blood cells},
volume = {80},
year = {2023}
}
@article{faucris.122076504,
abstract = {Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient-derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism. We found that knockdown of Drosophila M6, the sole member of the PLP family in flies, in the wing, and whole organism causes malformation and lethality, respectively. These phenotypes as well as the protrusions of patient-derived lymphoblastoid cells with increased GPM6A levels can be alleviated by cholesterol supplementation. Notably, overexpression as well as loss of M6 in neurons specifically compromises long-term memory in the courtship conditioning paradigm. Our findings thus indicate a critical role of correct GPM6A/M6 levels for cognitive function and support a role of the GPM6A duplication for the patient's phenotype. Together with other recent findings, this study highlights compromised cholesterol homeostasis as a recurrent feature in cognitive phenotypes.},
author = {Gregor, Anne and Kramer, Jamie M. and Van Der Voet, Monique and Schanze, Ina and Uebe, Steffen and Donders, Rogier and Reis, André and Schenck, Annette and Zweier, Christiane},
doi = {10.1002/humu.22697},
faupublication = {yes},
journal = {Human Mutation},
note = {EVALuna2:9228},
pages = {1495-505},
peerreviewed = {Yes},
title = {{Altered} {GPM6A}/{M6} {Dosage} {Impairs} {Cognition} and {Causes} {Phenotypes} {Responsive} to {Cholesterol} in {Human} and {Drosophila}},
volume = {35},
year = {2014}
}
@inproceedings{faucris.208385257,
author = {Berner, Daniel and Zenkel, Matthias and Pasutto, Francesca and Schoedel, Johannes and Reis, André and Kruse, Friedrich and Schlötzer-Schrehardt, Ursula},
faupublication = {yes},
note = {EVALuna2:34538},
peerreviewed = {Yes},
title = {{Alternative} splicing and nonsense-mediated {mRNA} decay contribute to regulation of {LOXL1} expression in response to cellular stress in pseudoexfoliation},
volume = {58},
year = {2017}
}
@article{faucris.212893241,
abstract = {Microglia are the main immune cells of the brain and express a large genetic pattern of genes linked to Parkinson's disease risk alleles. Monocytes like microglia are myeloid-lineage cells, raising the questions of the extent to which they share gene expression with microglia and whether they are already altered early in the clinical course of the disease. To decipher a monocytic gene expression signature in Parkinson's disease, we performed RNA-seq and applied the two-sample Kolmogorov-Smirnov test to identify differentially expressed genes between controls and patients with Parkinson's disease and changes in gene expression variability and dysregulation. The gene expression profiles of normal human monocytes and microglia showed a plethora of differentially expressed genes. Additionally, we identified a distinct gene expression pattern of monocytes isolated from Parkinson's disease patients at an early disease stage compared to controls using the Kolmogorov-Smirnov test. Differentially expressed genes included genes involved in immune activation such as HLA-DQB1, MYD88, REL, and TNF-alpha. Our data suggest that future studies of distinct leukocyte subsets are warranted to identify possible surrogate biomarkers and may lead to the identification of novel interventions early in the disease course.},
author = {Schlachetzki, Johannes and Prots, Iryna and Tao, Jenhan and Chun, Hyun B. and Saijo, Kaoru and Gosselin, David and Winner, Beate and Glass, Christopher K. and Winkler, Jürgen},
doi = {10.1038/s41598-018-28986-7},
faupublication = {yes},
journal = {Scientific Reports},
note = {EVALuna2:35780},
peerreviewed = {Yes},
title = {{A} monocyte gene expression signature in the early clinical course of {Parkinson}'s disease},
volume = {8},
year = {2018}
}
@article{faucris.252870970,
author = {Winner, Beate and Schlachetzki, Johannes C.M. and Prots, Iryna and Tao, Jenhan and Chun, Hyun B. and Saijo, Kaoru and Gosselin, David and Glass, Christopher K. and Winkler, Jürgen},
doi = {10.1038/s41598-020-62928-6},
faupublication = {yes},
journal = {Scientific Reports},
peerreviewed = {Yes},
title = {{A} monocyte gene expression signature in the early clinical course of {Parkinson}'s disease (vol 8, 10757, 2018)},
volume = {10},
year = {2020}
}
@article{faucris.123703624,
abstract = {AMPA-type glutamate receptors (AMPARs), key elements in excitatory neurotransmission in the brain, are macromolecular complexes whose properties and cellular functions are determined by the co-assembled constituents of their proteome. Here we identify AMPAR complexes that transiently form in the endoplasmic reticulum (ER) and lack the core-subunits typical for AMPARs in the plasma membrane. Central components of these ER AMPARs are the proteome constituents FRRS1l (C9orf4) and CPT1c that specifically and cooperatively bind to the pore-forming GluA1-4 proteins of AMPARs. Bi-allelic mutations in the human FRRS1L gene are shown to cause severe intellectual disability with cognitive impairment, speech delay and epileptic activity. Virus-directed deletion or overexpression of FRRS1l strongly impact synaptic transmission in adult rat brain by decreasing or increasing the number of AMPARs in synapses and extra-synaptic sites. Our results provide insight into the early biogenesis of AMPARs and demonstrate its pronounced impact on synaptic transmission and brain function.},
author = {Brechet, Aline and Buchert, Rebecca and Schwenk, Jochen and Boudkkazi, Sami and Zolles, Gerd and Siquier-Pernet, Karine and Schaber, Irene and Bildl, Wolfgang and Saadi, Abdelkrim and Bole-Feysot, Christine and Nitschke, Patrick and Reis, André and Sticht, Heinrich and Al-Sanna'A, Nouriya and Rolfs, Arndt and Kulik, Akos and Schulte, Uwe and Colleaux, Laurence and Abou Jamra, Rami and Fakler, Bernd},
doi = {10.1038/ncomms15910},
faupublication = {yes},
journal = {Nature Communications},
note = {EVALuna2:9374},
pages = {15910},
peerreviewed = {Yes},
title = {{AMPA}-receptor specific biogenesis complexes control synaptic transmission and intellectual ability},
volume = {8},
year = {2017}
}
@article{faucris.285665474,
abstract = {Huntington’s disease (HD) is a neurodegenerative disorder caused by poly-Q expansion in the Huntingtin (HTT) protein. Here, we delineate elevated mutant HTT (mHTT) levels in patient-derived cells including fibroblasts and iPSC derived cortical neurons using mesoscale discovery (MSD) HTT assays. HD patients’ fibroblasts and cortical neurons recapitulate aberrant alternative splicing as a molecular fingerprint of HD. Branaplam is a splicing modulator currently tested in a phase II study in HD (NCT05111249). The drug lowers total HTT (tHTT) and mHTT levels in fibroblasts, iPSC, cortical progenitors, and neurons in a dose dependent manner at an IC50 consistently below 10 nM without inducing cellular toxicity. Branaplam promotes inclusion of non-annotated novel exons. Among these Branaplam-induced exons, there is a 115 bp frameshift-inducing exon in the HTT transcript. This exon is observed upon Branaplam treatment in Ctrl and HD patients leading to a profound reduction of HTT RNA and protein levels. Importantly, Branaplam ameliorates aberrant alternative splicing in HD patients’ fibroblasts and cortical neurons. These findings highlight the applicability of splicing modulators in the treatment of CAG repeat disorders and decipher their molecular effects associated with the pharmacokinetic and -dynamic properties in patient-derived cellular models.},
author = {Krach, Florian and Stemick, Judith and Börstler, Tom and Weiss, Alexander and Lingos, Ioannis and Reischl, Stephanie and Meixner, Holger and Ploetz, Sonja and Farrell, Michaela and Hehr, Ute and Kohl, Zacharias and Winner, Beate and Winkler, Jürgen},
doi = {10.1038/s41467-022-34419-x},
faupublication = {yes},
journal = {Nature Communications},
note = {CRIS-Team Scopus Importer:2022-11-25},
pages = {6797},
peerreviewed = {Yes},
title = {{An} alternative splicing modulator decreases mutant {HTT} and improves the molecular fingerprint in {Huntington}’s disease patient neurons},
volume = {13},
year = {2022}
}
@article{faucris.221616853,
author = {Löhr, Sabine and Ekici, Arif Bülent and Uebe, Steffen and Büttner, Christian and Köhm, Michaela and Behrens, Frank and Böhm, Beate and Sticherling, Michael and Schett, Georg and Simon, David and Mössner, Rotraut and Nimeh, Ali and Oji, Vinzenz and Assmann, Gunter and Rech, Jürgen and Holmdahl, Rikard and Burkhardt, Harald and Reis, André and Hüffmeier, Ulrike},
doi = {10.1093/rheumatology/key448},
faupublication = {yes},
journal = {Rheumatology},
note = {CRIS-Team Scopus Importer:2019-07-02},
pages = {915-917},
peerreviewed = {Yes},
title = {{Analyses} of association of psoriatic arthritis and psoriasis vulgaris with functional {NCF1} variants},
volume = {58},
year = {2019}
}
@inproceedings{faucris.243947365,
address = {ROCKVILLE},
author = {Hirbo, Jibril and Pasutto, Francesca and Sealock, Julia and Evans, Patrick and Pawar, Priyanka and Tao, Ran and Straub, Peter and Breyer, Max and Berner, Daniel and Reis, André and Schlötzer-Schrehardt, Ursula and Khor, C. C. and Gamazon, Eric and Brantley, Milam A. and Joos, Karen M. and Cox, Nancy},
booktitle = {INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE},
doi = {10.21203/rs.3.rs-53203/v1},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2020-10-16},
peerreviewed = {unknown},
publisher = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
title = {{Analysis} of genetically determined gene expression suggest role of inflammatory processes in etiology of exfoliation syndrome},
year = {2020}
}
@article{faucris.290006803,
abstract = {Background: Exfoliation syndrome (XFS) is an age-related systemic disorder characterized by excessive production and progressive accumulation of abnormal extracellular material, with pathognomonic ocular manifestations. It is the most common cause of secondary glaucoma, resulting in widespread global blindness. The largest global meta-analysis of XFS in 123,457 multi-ethnic individuals from 24 countries identified seven loci with the strongest association signal in chr15q22–25 region near LOXL1. Expression analysis have so far correlated coding and a few non-coding variants in the region with LOXL1 expression levels, but functional effects of these variants is unclear. We hypothesize that analysis of the contribution of the genetically determined component of gene expression to XFS risk can provide a powerful method to elucidate potential roles of additional genes and clarify biology that underlie XFS. Results: Transcriptomic Wide Association Studies (TWAS) using PrediXcan models trained in 48 GTEx tissues leveraging on results from the multi-ethnic and European ancestry GWAS were performed. To eliminate the possibility of false-positive results due to Linkage Disequilibrium (LD) contamination, we i) performed PrediXcan analysis in reduced models removing variants in LD with LOXL1 missense variants associated with XFS, and variants in LOXL1 models in both multiethnic and European ancestry individuals, ii) conducted conditional analysis of the significant signals in European ancestry individuals, and iii) filtered signals based on correlated gene expression, LD and shared eQTLs, iv) conducted expression validation analysis in human iris tissues. We observed twenty-eight genes in chr15q22–25 region that showed statistically significant associations, which were whittled down to ten genes after statistical validations. In experimental analysis, mRNA transcript levels for ARID3B, CD276, LOXL1, NEO1, SCAMP2, and UBL7 were significantly decreased in iris tissues from XFS patients compared to control samples. TWAS genes for XFS were significantly enriched for genes associated with inflammatory conditions. We also observed a higher incidence of XFS comorbidity with inflammatory and connective tissue diseases. Conclusion: Our results implicate a role for connective tissues and inflammation pathways in the etiology of XFS. Targeting the inflammatory pathway may be a potential therapeutic option to reduce progression in XFS.},
author = {Hirbo, Jibril B. and Pasutto, Francesca and Gamazon, Eric R. and Evans, Patrick and Pawar, Priyanka and Berner, Daniel and Sealock, Julia and Tao, Ran and Straub, Peter S. and Konkashbaev, Anuar I. and Breyer, Max A. and Schlötzer-Schrehardt, Ursula and Wiesmann da Silva Reis, André and Brantley, Milam A. and Khor, Chiea C. and Joos, Karen M. and Cox, Nancy J.},
doi = {10.1186/s12864-023-09179-7},
faupublication = {yes},
journal = {BMC Genomics},
keywords = {Exfoliation syndrome; GTEx; GWAS; predicted expressions; transcriptomics; TWAS},
note = {CRIS-Team Scopus Importer:2023-03-03},
peerreviewed = {Yes},
title = {{Analysis} of genetically determined gene expression suggests role of inflammatory processes in exfoliation syndrome},
volume = {24},
year = {2023}
}
@article{faucris.203807783,
abstract = {Background: Haploinsufficiency of the class I bHLH transcription factor TCF4 causes Pitt-Hopkins syndrome (PTHS), a severe neurodevelopmental disorder, while common variants in the TCF4 gene have been identified as susceptibility factors for schizophrenia. It remains largely unknown, which brain regions are dependent on TCF4 for their development and function.
Methods: We systematically analyzed the expression pattern of TCF4 in the developing and adult mouse brain. We used immunofluorescent staining to identify candidate regions whose development and function depend on TCF4. In addition, we determined TCF4 expression in the developing rhesus monkey brain and in the developing and adult human brain through analysis of transcriptomic datasets and compared the expression pattern between species. Finally, we morphometrically and histologically analyzed selected brain structures in Tcf4-haploinsufficient mice and compared our morphometric findings to neuroanatomical findings in PTHS patients.
Results: TCF4 is broadly expressed in cortical and subcortical structures in the developing and adult mouse brain. The TCF4 expression pattern was highly similar between humans, rhesus monkeys, and mice. Moreover, Tcf4 haploinsufficiency in mice replicated structural brain anomalies observed in PTHS patients.
Conclusion: Our data suggests that TCF4 is involved in the development and function of multiple brain regions and indicates that its regulation is evolutionary conserved. Moreover, our data validate Tcf4-haploinsufficient mice as a model to study the neurodevelopmental basis of PTHS.},
author = {Jung, Matthias and Häberle, Benjamin and Tschaikowsky, Tristan and Wittmann, Marie-Theres and Balta, Elli-Anna and Stadler, Vivien-Charlott and Zweier, Christiane and Dörfler, Arnd and Gloeckner, Christian Johannes and Lie, Dieter Chichung},
doi = {10.1186/s13229-018-0200-1},
faupublication = {yes},
journal = {Molecular Autism },
note = {EVALuna:34022},
peerreviewed = {Yes},
title = {{Analysis} of the expression pattern of the schizophrenia-risk and intellectual disability gene {TCF4} in the developing and adult brain suggests a role in development and plasticity of cortical and hippocampal neurons},
volume = {9},
year = {2018}
}
@article{faucris.253939266,
abstract = {Improving quality of life (QoL) is central to amyotrophic lateral sclerosis (ALS) treatment. This Germany-wide, multicenter cross-sectional study analyses the impact of different symptom-specific treatments and ALS variants on QoL. Health-related QoL (HRQoL) in 325 ALS patients was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) and Eu-roQol Five Dimension Five Level Scale (EQ-5D-5L), together with disease severity (captured by the revised ALS Functional Rating Scale (ALSFRS-R)) and the current care and therapies used by our cohort. At inclusion, the mean ALSAQ-5 total score was 56.93 (max. 100, best = 0) with a better QoL associated with a less severe disease status (β = −1.96 per increase of one point in the ALSFRS-R score, p < 0.001). “Limb onset” ALS (lALS) was associated with a better QoL than “bulbar onset” ALS (bALS) (mean ALSAQ-5 total score 55.46 versus 60.99, p = 0.040). Moreover, with the ALSFRS-R as a covariate, using a mobility aid (β = −7.60, p = 0.001), being tracheostomized (β = −14.80, p = 0.004) and using non-invasive ventilation (β = –5.71, p = 0.030) were associated with an improved QoL, compared to those at the same disease stage who did not use these aids. In contrast, antide-pressant intake (β = 5.95, p = 0.007), and increasing age (β = 0.18, p = 0.023) were predictors of worse QoL. Our results showed that the ALSAQ-5 was better-suited for ALS patients than the EQ-5D-5L. Further, the early and symptom-specific clinical management and supply of assistive devices can significantly improve the individual HRQoL of ALS patients. Appropriate QoL questionnaires are needed to monitor the impact of treatment to provide the best possible and individualized care.},
author = {Peseschkian, Tara and Cordts, Isabell and Günther, René and Stolte, Benjamin and Zeller, Daniel and Schröter, Carsten and Weyen, Ute and Regensburger, Martin and Wolf, Joachim and Schneider, Ilka and Hermann, Andreas and Metelmann, Moritz and Kohl, Zacharias and Linker, Ralf A. and Koch, Jan Christoph and Büchner, Boriana and Weiland, Ulrike and Schönfelder, Erik and Heinrich, Felix and Osmanovic, Alma and Klopstock, Thomas and Dorst, Johannes and Ludolph, Albert C. and Boentert, Matthias and Hagenacker, Tim and Deschauer, Marcus and Lingor, Paul and Petri, Susanne and Schreiber-Katz, Olivia},
doi = {10.3390/brainsci11030372},
faupublication = {yes},
journal = {Brain Sciences},
keywords = {ALS treatment; Amyotrophic lateral sclerosis (ALS); Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5); Assistive devices; EuroQol Five Dimension Five Level Scale (EQ-5D-5L); Health-related quality of life (HRQoL); Quality of life (QoL); Symptom-specific treatment; “Bulbar onset” ALS (bALS); “Limb onset” ALS (lALS)},
note = {CRIS-Team Scopus Importer:2021-04-02},
peerreviewed = {Yes},
title = {{A} nation-wide, multi-center study on the quality of life of {ALS} patients in {Germany}},
volume = {11},
year = {2021}
}
@inproceedings{faucris.236251291,
address = {HOBOKEN},
author = {Spriewald, Bernd M. and Herrmann, Markus and Bach, Christian and Knaup, Karl and Krumbiegel, Mandy and Reis, André and Schiffer, Mario and Wiesener, Michael},
booktitle = {HLA},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2020-03-24},
pages = {313-313},
peerreviewed = {unknown},
publisher = {WILEY},
title = {{A} {NEW} {DIAGNOSTIC} {APPROACH} {TO} {HLA} {TESTING} {IN} {KIDNEY} {TRANSPLANT} {RECIPIENTS} {USING} {CULTURED} {URINE} {DERIVED} {TUBULAR} {CELLS}},
year = {2020}
}
@article{faucris.260662865,
abstract = {Antibody-mediated rejection (AMR) is a major obstacle to long-term kidney transplantation. AMR is mostly caused by donor specific HLA antibodies, which can arise before or any time after transplantation. Incomplete donor HLA typing and unavailability of donor DNA regularly preclude the assessment of donor-specificity of circulating anti-HLA antibodies. In our centre, this problem arises in approximately 20% of all post-transplant HLA-antibody assessments. We demonstrate that this diagnostic challenge can be resolved by establishing donor renal tubular cell cultures from recipient´s urine as a source of high-quality donor DNA. DNA was then verified for genetic origin and purity by fluorescence in situ hybridization and short tandem repeat analysis. Two representative cases highlight the diagnostic value of this approach which is corroborated by analysis of ten additional patients. The latter were randomly sampled from routine clinical care patients with available donor DNA as controls. In all 12 cases, we were able to perform full HLA typing of the respective donors confirmed by cross-comparison to results from the stored 10 donor DNAs. We propose that this noninvasive diagnostic approach for HLA typing in kidney transplant patients is valuable to determine donor specificity of HLA antibodies, which is important in clinical assessment of suspected AMR.},
author = {Bach, Christian and Knaup, Karl and Herrmann, Markus and Krumbiegel, Mandy and Pfister, Frederick and Büttner-Herold, Maike and Steffen, Martin and Zecher, Daniel and Lopau, Kai and Schneider, Karen and Dieterle, Anne and Amann, Kerstin Ute and Wiesmann da Silva Reis, André and Schiffer, Mario and Spriewald, Bernd and Wiesener, Michael S.},
doi = {10.1111/tri.13893},
faupublication = {yes},
journal = {Transplant International},
keywords = {antibody-mediated rejection; HLA typing; HLA-antibody post-transplantation; rejection},
note = {CRIS-Team Scopus Importer:2021-06-25},
peerreviewed = {Yes},
title = {{A} noninvasive diagnostic approach to retrospective donor {HLA} typing in kidney transplant patients using urine},
year = {2021}
}
@article{faucris.229006531,
abstract = {The SOXC transcription factors Sox4, Sox11 and Sox12, are critical neurodevelopmental regulators that are thought to function in a highly redundant fashion. Surprisingly, heterozygous missense mutations or deletions of SOX11 were recently detected in patients with Coffin-Siris syndrome-like syndrome (CSSLS), a neurodevelopmental disorder associated with intellectual disability, demonstrating that in humans SOX11 haploinsufficiency cannot be compensated and raising the question of the function of SOX11 in human neurodevelopment. Here, we describe the generation of SOX11(+/-) heterozygous human embryonic stem cell (hESC) lines by CRISPR/Cas9 genome engineering. SOX11 haploinsufficiency impaired the generation of neurons and resulted in a proliferation/differentiation imbalance of neural precursor cells and enhanced neuronal cell death. Using the SOX11(+/-) hESC model we provide for the first time experimental evidence that SOX11 haploinsufficiency is sufficient to impair key processes of human neurodevelopment, giving a first insight into the pathophysiology of CSSLS and SOX11 function in human neurodevelopment.},
author = {Turan, Sören and Börstler, Tom and Kavyanifar, Atria and Loskarn, Sandra and Reis, André and Winner, Beate and Lie, Dieter Chichung},
doi = {10.1093/hmg/ddz089},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {CRIS-Team WoS Importer:2019-11-12},
pages = {2589-2599},
peerreviewed = {Yes},
title = {{A} novel human stem cell model for {Coffin}-{Siris} syndrome-like syndrome reveals the importance of {SOX11} dosage for neuronal differentiation and survival},
volume = {28},
year = {2019}
}
@article{faucris.242707521,
abstract = {Bi-allelic loss-of-function variants in LAMC3, encoding extracellular matrix protein laminin gamma 3, represent a rare cause of occipital polymicrogyria with epilepsy, developmental delay and cognitive impairment. So far, only five families have been reported. We now identified a novel, homozygous splice variant in LAMC3 in an individual with an unusual manifestation of cortical malformation. She presented with polymicrogyria in the frontal but not the occipital lobes, with adult-onset seizures and normal psychomotor development and cognition. Additionally, ictal asystole, requiring implantation of a pacemaker, and nonepileptic seizures occurred. This case expands the spectrum of LAMC3-associated cortical malformation phenotypes to frontal only polymicrogyria and adult-onset of epilepsy.},
author = {Kasper, Burkhard and Kraus, Cornelia and Schwarz, Michael and Rösch, Julie and Thiel, Christian and Reis, André and Zweier, Christiane},
doi = {10.1002/ajmg.a.61846},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
keywords = {cortical malformation; epilepsy; LAMC3; polymicrogyria; seizures},
note = {CRIS-Team Scopus Importer:2020-09-18},
peerreviewed = {Yes},
title = {{A} novel splice variant expands the {LAMC3}-associated cortical phenotype to frontal only polymicrogyria and adult-onset epilepsy},
year = {2020}
}
@article{faucris.109341804,
abstract = {Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1, also known as CEP90, and C21orf2, also known as LRRC76, as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2 variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease.},
author = {Wheway, Gabrielle and Schmidts, Miriam and Mans, Dorus A. and Szymanska, Katarzyna and Nguyen, Thanh-Minh T. and Racher, Hilary and Phelps, Ian G. and Toedts, Grischa and Kennedy, Julie and Wunderlich, Kirsten A. and Sorusch, Nasrin and Abdelhamed, Zakia A. and Natarajan, Subaashini and Herridge, Warren and Van Reeuwijk, Jeroen and Horn, Nicola and Boldt, Karsten and Parry, David A. and Letteboer, Stef J. F. and Roosing, Susanne and Adams, Matthew and Bell, Sandra M. and Bond, Jacquelyn and Higgins, Julie and Morrison, Ewan E. and Tomlinson, Darren C. and Slaats, Gisela G. and Van Dam, Teunis J. P. and Huang, Lijia and Keßler, Kristin and Gießl, Andreas and Logan, Clare V. and Boyle, Evan A. and Shendure, Jay and Anazi, Shamsa and Aldahmesh, Mohammed and Al Hazzaa, Selwa and Hegele, Robert A. and Ober, Carole and Frosk, Patrick and Mhanni, Aizeddin A. and Chodirker, Bernard N. and Chudley, Albert E. and Lamont, Ryan and Bernier, Francois P. and Beaulieu, Chandree L. and Gordon, Paul and Pon, Richard T. and Donahue, Clem and Barkovich, A. James and Wolf, Louis and Toomes, Carmel and Thiel, Christian and Boycott, Kym M. and Mckibbin, Martin and Inglehearn, Chris F. and Stewart, Fiona and Omran, Heymut and Huynen, Martijn A. and Sergouniotis, Panagiotis I. and Alkuraya, Fowzan S. and Parboosingh, Jillian S. and Innes, A. Micheil and Willoughby, Cohn E. and Giles, Rachel H. and Webster, Andrew R. and Ueffing, Marius and Blacque, Oliver and Gleeson, Joseph G. and Wolfrum, Uwe and Beales, Philip L. and Gibson, Toby and Doherty, Dan and Mitchison, Hannah M. and Roepman, Ronald and Johnson, Colin A.},
doi = {10.1038/ncb3201},
faupublication = {yes},
journal = {Nature Cell Biology},
note = {EVALuna2:9277},
pages = {1074-87},
peerreviewed = {Yes},
title = {{An} {siRNA}-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes},
volume = {17},
year = {2015}
}
@article{faucris.282419491,
abstract = {Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease characterized by adaptive immune system activation, formation of double-stranded DNA autoantibodies and organ inflammation. Five patients with SLE (four women and one man) with a median (range) age of 22 (6) years, median (range) disease duration of 4 (8) years and active disease (median (range) SLE disease activity index Systemic Lupus Erythematosus Disease Activity Index: 16 (8)) refractory to several immunosuppressive drug treatments were enrolled in a compassionate-use chimeric antigen receptor (CAR) T cell program. Autologous T cells from patients with SLE were transduced with a lentiviral anti-CD19 CAR vector, expanded and reinfused at a dose of 1 × 106 CAR T cells per kg body weight into the patients after lymphodepletion with fludarabine and cyclophosphamide. CAR T cells expanded in vivo, led to deep depletion of B cells, improvement of clinical symptoms and normalization of laboratory parameters including seroconversion of anti-double-stranded DNA antibodies. Remission of SLE according to DORIS criteria was achieved in all five patients after 3 months and the median (range) Systemic Lupus Erythematosus Disease Activity Index score after 3 months was 0 (2). Drug-free remission was maintained during longer follow-up (median (range) of 8 (12) months after CAR T cell administration) and even after the reappearance of B cells, which was observed after a mean (±s.d.) of 110 ± 32 d after CAR T cell treatment. Reappearing B cells were naïve and showed non-class-switched B cell receptors. CAR T cell treatment was well tolerated with only mild cytokine-release syndrome. These data suggest that CD19 CAR T cell transfer is feasible, tolerable and highly effective in SLE.},
author = {Mackensen, Andreas and Müller, Fabian and Mougiakakos, Dimitrios and Böltz, Sebastian and Wilhelm, Artur and Aigner, Michael and Völkl, Simon and Simon, David and Kleyer, Arnd and Munoz, Luis Enrique and Kretschmann, Sascha and Kharboutli, Soraya and Gary, Regina and Reimann, Hannah and Rösler, Wolf and Uderhardt, Stefan and Bang, Holger and Herrmann, Martin and Ekici, Arif Bülent and Büttner, Christian and Habenicht, Katharina Marie and Winkler, Thomas and Krönke, Gerhard and Schett, Georg},
doi = {10.1038/s41591-022-02017-5},
faupublication = {yes},
journal = {Nature Medicine},
note = {CRIS-Team Scopus Importer:2022-09-30},
peerreviewed = {Yes},
title = {{Anti}-{CD19} {CAR} {T} cell therapy for refractory systemic lupus erythematosus},
year = {2022}
}
@article{faucris.123985664,
abstract = {Rhizomelic chondrodysplasia punctata (RCDP) is a group of disorders with overlapping clinical features including rhizomelia, chondrodysplasia punctata, coronal clefts, cervical dysplasia, congenital cataracts, profound postnatal growth retardation, severe intellectual disability, and seizures. Mutations in PEX7, GNPAT, and AGPS, all involved in the plasmalogen-biosynthesis pathway, have been described in individuals with RCDP. Here, we report the identification of mutations in another gene in plasmalogen biosynthesis, fatty acyl-CoA reductase 1 (FAR1), in two families affected by severe intellectual disability, early-onset epilepsy, microcephaly, congenital cataracts, growth retardation, and spasticity. Exome analyses revealed a homozygous in-frame indel mutation (c.495{\_}507delinsT [p.Glu165{\_}Pro169delinsAsp]) in two siblings from a consanguineous family and compound-heterozygous mutations (c.[787C>T];[1094A>G], p.[Arg263(*)];[Asp365Gly]) in a third unrelated individual. FAR1 reduces fatty acids to their respective fatty alcohols for the plasmalogen-biosynthesis pathway. To assess the pathogenicity of the identified mutations, we transfected human embryonic kidney 293 cells with plasmids encoding FAR1 with either wild-type or mutated constructs and extracted the lipids from the cells. We screened the lipids with gas chromatography and mass spectrometry and found that all three mutations abolished the reductase activity of FAR1, given that no fatty alcohols could be detected. We also observed reduced plasmalogens in red blood cells in one individual to a range similar to that seen in individuals with RCDP, further supporting abolished FAR1 activity. We thus expand the spectrum of clinical features associated with defects in plasmalogen biosynthesis to include FAR1 deficiency as a cause of syndromic severe intellectual disability with cataracts, epilepsy, and growth retardation but without rhizomelia.},
author = {Buchert, Rebecca and Tawamie, Hasan and Smith, Christopher and Uebe, Steffen and Innes, A. Micheil and Al Hallak, Bassam and Ekici, Arif Bülent and Sticht, Heinrich and Schwarze, Bernd and Lamont, Ryan E. and Parboosingh, Jillian S. and Bernier, Francois P. and Abou Jamra, Rami},
doi = {10.1016/j.ajhg.2014.10.003},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9238},
pages = {602-10},
peerreviewed = {Yes},
title = {{A} {Peroxisomal} {Disorder} of {Severe} {Intellectual} {Disability}, {Epilepsy}, and {Cataracts} {Due} to {Fatty} {Acyl}-{CoA} {Reductase} 1 {Deficiency}},
volume = {95},
year = {2014}
}
@article{faucris.116656364,
abstract = {PTEN hamartoma tumour syndrome (PHTS) is caused by heterozygous variants in PTEN and is characterised by tumour predisposition, macrocephaly, and cognition impairment. Bi-allelic loss of PTEN activity has not been reported so far and animal models suggest that bi-allelic loss of PTEN activity is embryonically lethal. Here, we report the identification of a novel homozygous variant in PTEN, NM{\_}000314.4; c.545T>C; p.Leu182Ser, in two adolescent siblings with severe macrocephaly and mild intellectual disability. The variant is predicted to be damaging and is associated with significantly increased phospho-S6 downstream of PTEN. The absence of tumours in the two homozygous siblings as well as lack of symptoms of PHTS in the heterozygous carriers of the family suggest that this particular variant is functionally hypomorphic rather than deleterious.European Journal of Human Genetics advance online publication, 7 October 2015; doi:10.1038/ejhg.2015.209.},
author = {Schwerd, Tobias and Khaled, Andrea V. and Schürmann, Manfred and Chen, Hannah and Händel, Norman and Reis, André and Gillessen-Kaesbach, Gabriele and Uhlig, Holm H. and Abou Jamra, Rami},
doi = {10.1038/ejhg.2015.209},
faupublication = {yes},
journal = {European journal of human genetics},
note = {EVALuna2:9252},
peerreviewed = {Yes},
title = {{A} recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of {PTEN} hamartoma tumour syndrome},
year = {2015}
}
@article{faucris.314825333,
abstract = {Sporadic Parkinson’s Disease (sPD) is a progressive neurodegenerative disorder caused by multiple genetic and environmental factors. Mitochondrial dysfunction is one contributing factor, but its role at different stages of disease progression is not fully understood. Here, we showed that neural precursor cells and dopaminergic neurons derived from induced pluripotent stem cells (hiPSCs) from sPD patients exhibited a hypometabolism. Further analysis based on transcriptomics, proteomics, and metabolomics identified the citric acid cycle, specifically the α-ketoglutarate dehydrogenase complex (OGDHC), as bottleneck in sPD metabolism. A follow-up study of the patients approximately 10 years after initial biopsy demonstrated a correlation between OGDHC activity in our cellular model and the disease progression. In addition, the alterations in cellular metabolism observed in our cellular model were restored by interfering with the enhanced SHH signal transduction in sPD. Thus, inhibiting overactive SHH signaling may have potential as neuroprotective therapy during early stages of sPD.},
author = {Schmidt, Sebastian and Stautner, Constantin and Vu, Duc Tung and Heinz, Alexander and Regensburger, Martin and Karayel, Ozge and Trümbach, Dietrich and Artati, Anna and Kaltenhäuser, Sabine and Nassef, Mohamed Zakaria and Hembach, Sina and Steinert, Letyfee and Winner, Beate and Winkler, Jürgen and Jastroch, Martin and Luecken, Malte D. and Theis, Fabian J. and Westmeyer, Gil Gregor and Adamski, Jerzy and Mann, Matthias and Hiller, Karsten and Giesert, Florian and Vogt Weisenhorn, Daniela M. and Wurst, Wolfgang},
doi = {10.1038/s41467-023-42862-7},
faupublication = {yes},
journal = {Nature Communications},
note = {CRIS-Team Scopus Importer:2023-12-08},
peerreviewed = {Yes},
title = {{A} reversible state of hypometabolism in a human cellular model of sporadic {Parkinson}’s disease},
volume = {14},
year = {2023}
}
@article{faucris.242103753,
abstract = {Arginase 1 (Arg1), which converts L-arginine into ornithine and urea, exerts pleiotropic immunoregulatory effects. However, the function of Arg1 in inflammatory bowel disease (IBD) remains poorly characterized. Here, we found that Arg1 expression correlated with the degree of inflammation in intestinal tissues from IBD patients. In mice, Arg1 was upregulated in an IL-4-/IL-13- and intestinal microbiota-dependent manner. Tie2-Cre+/-Arg1fl/fl mice lacking Arg1 in hematopoietic and endothelial cells recovered faster from experimental colitis than Arg1-expressing littermates. This correlated with decreased vessel density, compositional changes in intestinal microbiota, diminished infiltration by myeloid cells and an accumulation of intraluminal polyamines that promote epithelial healing. The pro-resolving effect of Arg1-deletion was reduced by an L-arginine-free diet, but rescued by simultaneous deletion of other L-arginine-metabolizing enzymes such as Arg2 or Nos2, demonstrating that protection from colitis requires L-arginine. Fecal microbiota transfers from Tie2-Cre+/-Arg1fl/fl mice into wild-type recipients ameliorated intestinal inflammation while transfers from wild-type littermates into Arg1-deficient mice prevented an advanced recovery from colitis. Thus, an increased availability of L-arginine as well as altered intestinal microbiota and metabolic products account for the accelerated resolution from colitis in the absence of Arg1. Consequently, the metabolism of L-arginine may serve as target for clinical intervention in IBD patients.
−1 per 1.73 m2 or overt proteinuria, serum osteoprotegerin (OPG), C-terminal fibroblast growth factor-23 (FGF23), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), cross-linked C-telopeptide of type 1 collagen (CTX1), procollagen 1 intact N-terminal propeptide (P1NP), phosphate, calcium, and 25-OH vitamin D were measured at baseline. Participants with missing values among these parameters (n = 971) were excluded, leaving a total of 4 246 participants for analysis. During a median follow-up of 6.5 years, 387 non-CV deaths, 173 CV deaths, 645 nonfatal major adverse CV events (MACEs) and 368 hospitalizations for congestive heart failure (CHF) were observed. OPG and FGF23 were associated with all outcomes, with the highest hazard ratios (HRs) for OPG. In the final Cox regression model, adjusted for CV risk factors, including kidney function and all other investigated biomarkers, each standard deviation increase in OPG was associated with non-CV death (HR 1.76, 95% CI: 1.35–2.30), CV death (HR 2.18, 95% CI: 1.50–3.16), MACE (HR 1.38, 95% CI: 1.12–1.71) and hospitalization for CHF (HR 2.05, 95% CI: 1.56–2.69). Out of the nine biomarkers examined, stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.},
author = {Reimer, Katharina Charlotte and Nadal, Jennifer and Meiselbach, Heike and Schmid, Matthias and Schultheiss, Ulla T. and Kotsis, Fruzsina and Stockmann, Helena and Friedrich, Nele and Nauck, Matthias and Krane, Vera and Eckardt, Kai-Uwe and Schneider, Markus and Kramann, Rafael and Floege, Jürgen and Saritas, Turgay and Schiffer, Mario and Prokosch, Hans-Ulrich and Bärthlein, Barbara and Beck, Andreas and Reis, André and Ekici, Arif Bülent and Becker, Susanne and Alberth-Schmidt, Ulrike and Weigel, Anke and Marschall, Sabine and Schefler, Eugenia and Walz, Gerd and Köttgen, Anna and Meder, Simone and Mitsch, Erna and Reinhard, Ursula and Schaeffner, Elke and Baid-Agrawal, Seema and Theisen, Kerstin and Schmidt-Ott, Kai and Zeier, Martin and Sommerer, Claudia and Aykac, Mehtap and Wolf, Gunter and Paul, Rainer and Börner-Klein, Antje and Bauer, Britta and Raschenberger, Julia and Kollerits, Barbara and Forer, Lukas and Schönherr, Sebastian and Weissensteiner, Hansi and Oefner, Peter and Gronwald, Wolfram},
doi = {10.1038/s41413-023-00291-8},
faupublication = {yes},
journal = {Bone Research},
note = {CRIS-Team Scopus Importer:2023-11-10},
peerreviewed = {Yes},
title = {{Association} of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the {German} {Chronic} {Kidney} {Disease} ({GCKD}) cohort},
volume = {11},
year = {2023}
}
@article{faucris.251039397,
abstract = {Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P <.001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P <.001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.},
author = {Li, Zheng and Wang, Zhenxun and Lee, Mei Chin and Zenkel, Matthias and Peh, Esther and Ozaki, Mineo and Topouzis, Fotis and Nakano, Satoko and Chan, Anita and Chen, Shuwen and Williams, Susan E.I. and Orr, Andrew and Nakano, Masakazu and Kobakhidze, Nino and Zarnowski, Tomasz and Popa-Cherecheanu, Alina and Mizoguchi, Takanori and Manabe, Shin Ichi and Hayashi, Ken and Kazama, Shigeyasu and Inoue, Kenji and Mori, Yosai and Miyata, Kazunori and Sugiyama, Kazuhisa and Higashide, Tomomi and Chihara, Etsuo and Ideta, Ryuichi and Ishiko, Satoshi and Yoshida, Akitoshi and Tokumo, Kana and Kiuchi, Yoshiaki and Ohashi, Tsutomu and Sakurai, Toshiya and Sugimoto, Takako and Chuman, Hideki and Aihara, Makoto and Inatani, Masaru and Mori, Kazuhiko and Ikeda, Yoko and Ueno, Morio and Gaston, Daniel and Rafuse, Paul and Shuba, Lesya and Saunders, Joseph and Nicolela, Marcelo and Chichua, George and Tabagari, Sergo and Founti, Panayiota and Sim, Kar Seng and Meah, Wee Yang and Soo, Hui Meng and Chen, Xiao Yin and Chatzikyriakidou, Anthi and Keskini, Christina and Pappas, Theofanis and Anastasopoulos, Eleftherios and Lambropoulos, Alexandros and Panagiotou, Evangelia S. and Mikropoulos, Dimitrios G. and Kosior-Jarecka, Ewa and Cheong, Augustine and Li, Yuanhan and Lukasik, Urszula and Nongpiur, Monisha E. and Husain, Rahat and Perera, Shamira A. and Álvarez, Lydia and García, Montserrat and González-Iglesias, Héctor and Cueto, Andrés F.V. and Cueto, Luis F.V. and Martinón-Torres, Federico and Salas, Antonio and Oguz, Çilingir and Tamcelik, Nevbahar and Atalay, Eray and Batu, Bilge and Irkec, Murat and Aktas, Dilek and Kasim, Burcu and Astakhov, Yury S. and Astakhov, Sergei Y. and Akopov, Eugeny L. and Gießl, Andreas and Mardin, Christian Y. and Hellerbrand, Claus and Cooke Bailey, Jessica N. and Igo, Robert P. and Haines, Jonathan L. and Edward, Deepak P. and Heegaard, Steffen and Davila, Sonia and Tan, Patrick and Kang, Jae H. and Pasquale, Louis R. and Kruse, Friedrich and Reis, André and Carmichael, Trevor R. and Hauser, Michael and Ramsay, Michele and Mossböck, Georg and Yildirim, Nilgun and Tashiro, Kei and Konstas, Anastasios G.P. and Coca-Prados, Miguel and Foo, Jia Nee and Kinoshita, Shigeru and Sotozono, Chie and Kubota, Toshiaki and Dubina, Michael and Ritch, Robert and Wiggs, Janey L. and Pasutto, Francesca and Schlötzer-Schrehardt, Ursula and Ho, Ying Swan and Aung, Tin and Tam, Wai Leong and Khor, Chiea Chuen},
doi = {10.1001/jama.2021.0507},
faupublication = {yes},
journal = {Journal of the American Medical Association},
note = {CRIS-Team Scopus Importer:2021-03-05},
pages = {753-764},
peerreviewed = {Yes},
title = {{Association} of {Rare} {CYP39A1} {Variants} with {Exfoliation} {Syndrome} {Involving} the {Anterior} {Chamber} of the {Eye}},
volume = {325},
year = {2021}
}
@article{faucris.273955323,
abstract = {Astrocytes are highly abundant in the mammalian brain, and their functions are of vital importance for all aspects of development, adaption, and aging of the central nervous system (CNS). Mounting evidence indicates the important contributions of astrocytes to a wide range of neuropathies. Still, our understanding of astrocyte development significantly lags behind that of other CNS cells. We here combine immunohistochemical approaches with genetic fate-mapping, behavioral paradigms, single-cell transcriptomics, and in vivo two-photon imaging, to comprehensively assess the generation and the proliferation of astrocytes in the dentate gyrus (DG) across the life span of a mouse. Astrogenesis in the DG is initiated by radial glia-like neural stem cells giving rise to locally dividing astrocytes that enlarge the astrocyte compartment in an outside-in-pattern. Also in the adult DG, the vast majority of astrogenesis is mediated through the proliferation of local astrocytes. Interestingly, locally dividing astrocytes were able to adapt their proliferation to environmental and behavioral stimuli revealing an unexpected plasticity. Our study establishes astrocytes as enduring plastic elements in DG circuits, implicating a vital contribution of astrocyte dynamics to hippocampal plasticity.},
author = {Schneider, Julia and Weigel, Johannes and Wittmann, Marie-Theres and Svehla, Pavel and Ehrt, Sebastian and Zheng, Fang and Elmzzahi, Tarek and Karpf, Julian and Paniagua-Herranz, Lucia and Basak, Onur and Ekici, Arif Bülent and Wiesmann da Silva Reis, André and Alzheimer, Christian and Ortega De La O, Felipe and Liebscher, Sabine and Beckervordersandforth-Bonk, Ruth},
doi = {10.15252/embj.2021110409},
faupublication = {yes},
journal = {EMBO Journal},
note = {CRIS-Team WoS Importer:2022-04-29},
peerreviewed = {Yes},
title = {{Astrogenesis} in the murine dentate gyrus is a life-long and dynamic process},
year = {2022}
}
@article{faucris.237476607,
abstract = {An amendment to this paper has been published and can be accessed via a link at the top of the paper.},
author = {Schlachetzki, Johannes and Prots, Iryna and Tao, Jenhan and Chun, Hyun B. and Saijo, Kaoru and Gosselin, David and Winner, Beate and Glass, Christopher K. and Winkler, Jürgen},
doi = {10.1038/s41598-020-62928-6},
faupublication = {yes},
journal = {Scientific Reports},
note = {CRIS-Team Scopus Importer:2020-04-17},
peerreviewed = {Yes},
title = {{Author} {Correction}: {A} monocyte gene expression signature in the early clinical course of {Parkinson}’s disease ({Scientific} {Reports}, (2018), 8, 1, (10757), 10.1038/s41598-018-28986-7)},
volume = {10},
year = {2020}
}
@article{faucris.230818773,
author = {Blok, Lot Snijders and Rousseau, Justine and Twist, Joanna and Ehresmann, Sophie and Takaku, Motoki and Venselaar, Hanka and Rodan, Lance H. and Nowak, Catherine B. and Douglas, Jessica and Swoboda, Kathryn J. and Steeves, Marcie A. and Sahai, Inderneel and Stumpel, Connie T. R. M. and Stegmann, Alexander P. A. and Wheeler, Patricia and Willing, Marcia and Fiala, Elise and Kochhar, Aaina and Gibson, William T. and Cohen, Ana S. A. and Agbahovbe, Ruky and Innes, A. Micheil and Au, P. Y. Billie and Rankin, Julia and Anderson, Ilse J. and Skinner, Steven A. and Louie, Raymond J. and Warren, Hannah E. and Afenjar, Alexandra and Keren, Boris and Nava, Caroline and Buratti, Julien and Isapof, Arnaud and Rodriguez, Diana and Lewandowski, Raymond and Propst, Jennifer and Van Essen, Ton and Choi, Murim and Lee, Sangmoon and Chae, Jong H. and Price, Susan and Schnur, Rhonda E. and Douglas, Ganka and Wentzensen, Ingrid M. and Zweier, Christiane and Reis, André and Bialer, Martin G. and Moore, Christine and Koopmans, Marije and Brilstra, Eva H. and Monroe, Glen R. and Van Gassen, Koen L. I. and Van Binsbergen, Ellen and Newbury-Ecob, Ruth and Bownass, Lucy and Bader, Ingrid and Mayr, Johannes A. and Wortmann, Saskia B. and Jakielski, Kathy J. and Strand, Edythe A. and Kloth, Katja and Bierhals, Tatjana and Roberts, John D. and Petrovich, Robert M. and Machida, Shinichi and Kurumizaka, Hitoshi and Lelieveld, Stefan and Pfundt, Rolph and Jansen, Sandra and Deriziotis, Pelagia and Faivre, Laurence and Thevenon, Julien and Assoum, Mirna and Shriberg, Lawrence and Kleefstra, Tjitske and Brunner, Han G. and Wade, Paul A. and Fisher, Simon E. and Campeau, Philippe M. and Mcrae, Jeremy F. and Clayton, Stephen and Fitzgerald, Tomas W. and Kaplanis, Joanna and Prigmore, Elena and Rajan, Diana and Sifrim, Alejandro and Aitken, Stuart and Akawi, Nadia and Alvi, Mohsan and Ambridge, Kirsty and Barrett, Daniel M. and Bayzetinova, Tanya and Jones, Philip and Jones, Wendy D. and King, Daniel and Krishnappa, Netravathi and Mason, Laura E. and Singh, Tarjinder and Tivey, Adrian R. and Ahmed, Munaza and Anjum, Uruj and Archer, Hayley and Armstrong, Ruth and Awada, Jana and Balasubramanian, Meena and Banka, Siddharth and Baralle, Diana and Barnicoat, Angela and Batstone, Paul and Baty, David and Bennett, Chris and Berg, Jonathan and Bernhard, Birgitta and Bevan, A. Paul and Bitner-Glindzicz, Maria and Blair, Edward and Blyth, Moira and Bohanna, David and Bourdon, Louise and Bourn, David and Bradley, Lisa and Brady, Angela and Brent, Simon and Brewer, Carole and Brunstrom, Kate and Bunyan, David J. and Burn, John and Canham, Natalie and Castle, Bruce and Chandler, Kate and Chatzimichali, Elena and Cilliers, Deirdre and Clarke, Angus and Clasper, Susan and Clayton-Smith, Jill and Clowes, Virginia and Coates, Andrea and Cole, Trevor and Colgiu, Irina and Collins, Amanda and Collinson, Morag N. and Connell, Fiona and Cooper, Nicola and Cox, Helen and Cresswell, Lara and Cross, Gareth and Crow, Yanick and D'Alessandro, Mariella and Dabir, Tabib and Davidson, Rosemarie and Davies, Sally and De Vries, Dylan and Dean, John and Deshpande, Charu and Devlin, Gemma and Dixit, Abhijit and Dobbie, Angus and Donaldson, Alan and Donnai, Dian and Donnelly, Deirdre and Donnelly, Carina and Douglas, Angela and Douzgou, Sofia and Duncan, Alexis and Eason, Jacqueline and Ellard, Sian and Ellis, Ian and Elmslie, Frances and Evans, Karenza and Everest, Sarah and Fendick, Tina and Fisher, Richard and Flinter, Frances and Foulds, Nicola and Fry, Andrew and Fryer, Alan and Gardiner, Carol and Gaunt, Lorraine and Ghali, Neeti and Gibbons, Richard and Gill, Harinder and Goodship, Judith and Goudie, David and Gray, Emma and Green, Andrew and Greene, Philip and Greenhalgh, Lynn and Gribble, Susan and Harrison, Rachel and Harrison, Lucy and Harrison, Victoria and Hawkins, Rose and He, Liu and Hellens, Stephen and Henderson, Alex and Hewitt, Sarah and Hildyard, Lucy and Hobson, Emma and Holden, Simon and Holder, Muriel and Holder, Susan and Hollingsworth, Georgina and Homfray, Tessa and Humphreys, Mervyn and Hurst, Jane and Hutton, Ben and Ingram, Stuart and Irving, Melita and Islam, Lily and Jackson, Andrew and Jarvis, Joanna and Jenkins, Lucy and Johnson, Diana and Jones, Elizabeth and Josifova, Dragana and Joss, Shelagh and Kaemba, Beckie and Kazembe, Sandra and Kelsell, Rosemary and Kerr, Bronwyn and Kingston, Helen and Kini, Usha and Kinning, Esther and Kirby, Gail and Kirk, Claire and Kivuva, Emma and Kraus, Alison and Kumar, Dhavendra and Kumar, V. K. Ajith and Lachlan, Katherine and Lam, Wayne and Lampe, Anne and Langman, Caroline and Lees, Melissa and Lim, Derek and Longman, Cheryl and Lowther, Gordon and Lynch, Sally A. and Magee, Alex and Maher, Eddy and Male, Alison and Mansour, Sahar and Marks, Karen and Martin, Katherine and Maye, Una and Mccann, Emma and Mcconnell, Vivienne and Mcentagart, Meriel and Mcgowan, Ruth and Mckay, Kirsten and Mckee, Shane and Mcmullan, Dominic J. and Mcnerlan, Susan and Mcwilliam, Catherine and Mehta, Sarju and Metcalfe, Kay and Middleton, Anna and Miedzybrodzka, Zosia and Miles, Emma and Mohammed, Shehla and Montgomery, Tara and Moore, David and Morgan, Sian and Morton, Jenny and Mugalaasi, Hood and Murday, Victoria and Murphy, Helen and Naik, Swati and Nemeth, Andrea and Nevitt, Louise and Norman, Andrew and O'Shea, Rosie and Ogilvie, Caroline and Ong, Kai-Ren and Park, Soo-Mi and Parker, Michael J. and Patel, Chirag and Paterson, Joan and Payne, Stewart and Perrett, Daniel and Phipps, Julie and Pilz, Daniela T. and Pollard, Martin and Pottinger, Caroline and Poulton, Joanna and Pratt, Norman and Prescott, Katrina and Pridham, Abigail and Procter, Annie and Purnell, Hellen and Quarrell, Oliver and Ragge, Nicola and Rahbari, Raheleh and Randall, Josh and Raymond, Lucy and Rice, Debbie and Robert, Leema and Roberts, Eileen and Roberts, Jonathan and Roberts, Paul and Roberts, Gillian and Ross, Alison and Rosser, Elisabeth and Saggar, Anand and Samant, Shalaka and Sampson, Julian and Sandford, Richard and Sarkar, Ajoy and Schweiger, Susann and Scott, Richard and Scurr, Ingrid and Selby, Ann and Seller, Anneke and Sequeira, Cheryl and Shannon, Nora and Sharif, Saba and Shaw-Smith, Charles and Shearing, Emma and Shears, Debbie and Sheridan, Eamonn and Simonic, Ingrid and Singzon, Roldan and Skitt, Zara and Smith, Audrey and Smith, Kath and Smithson, Sarah and Sneddon, Linda and Splitt, Miranda and Squires, Miranda and Stewart, Fiona and Stewart, Helen and Straub, Volker and Suri, Mohnish and Sutton, Vivienne and Swaminathan, Ganesh Jawahar and Sweeney, Elizabeth and Tatton-Brown, Kate and Taylor, Cat and Taylor, Rohan and Tein, Mark and Temple, I. Karen and Thomson, Jenny and Tischkowitz, Marc and Tomkins, Susan and Torokwa, Audrey and Treacy, Becky and Turner, Claire and Turnpenny, Peter and Tysoe, Carolyn and Vandersteen, Anthony and Varghese, Vinod and Vasudevan, Pradeep and Vijayarangakannan, Parthiban and Vogt, Julie and Wakeling, Emma and Wallwark, Sarah and Waters, Jonathon and Weber, Astrid and Wellesley, Diana and Whiteford, Margo and Widaa, Sara and Wilcox, Sarah and Wilkinson, Emily and Williams, Denise and Williams, Nicola and Wilson, Louise and Woods, Geoff and Wragg, Christopher and Wright, Michael and Yates, Laura and Yau, Michael and Nellaker, Chris and Parker, Michael and Firth, Helen V. and Wright, Caroline F. and Fitzpatrick, David R. and Barrett, Jeffrey C. and Hurles, Matthew E.},
doi = {10.1038/s41467-019-08800-2},
faupublication = {yes},
journal = {Nature Communications},
note = {EVALuna2:206986},
peerreviewed = {No},
title = {{Author} {Correction}: {CHD3} helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language},
volume = {10},
year = {2019}
}
@article{faucris.121970904,
abstract = {Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development.},
author = {Boycott, Kym M. and Beaulieu, Chandree L. and Kernohan, Kristin D. and Gebril, Ola H. and Mhanni, Aziz and Chudley, Albert E. and Redl, David and Qin, Wen and Hampson, Sarah and Kuery, Sebastien and Tetreault, Martine and Puffenberger, Erik G. and Scott, James N. and Bezieau, Stephane and Reis, André and Uebe, Steffen and Schumacher, Johannes and Hegele, Robert A. and Mcleod, D. Ross and Galvez-Peralta, Marina and Majewski, Jacek and Ramaekers, Vincent T. and Nebert, Daniel W. and Innes, A. Micheil and Parboosingh, Jillian S. and Abou Jamra, Rami},
doi = {10.1016/j.ajhg.2015.11.002},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9292},
pages = {886-93},
peerreviewed = {Yes},
title = {{Autosomal}-{Recessive} {Intellectual} {Disability} with {Cerebellar} {Atrophy} {Syndrome} {Caused} by {Mutation} of the {Manganese} and {Zinc} {Transporter} {Gene} {SLC39A8}},
volume = {97},
year = {2015}
}
@article{faucris.121082984,
abstract = {The tRNA splicing endonuclease is a highly evolutionarily conserved protein complex, involved in the cleavage of intron-containing tRNAs. In human it consists of the catalytic subunits TSEN2 and TSEN34, as well as the non-catalytic TSEN54 and TSEN15. Recessive mutations in the corresponding genes of the first three are known to cause pontocerebellar hypoplasia (PCH) types 2A-C, 4, and 5. Here, we report three homozygous TSEN15 variants that cause a milder version of PCH2. The affected individuals showed progressive microcephaly, delayed developmental milestones, intellectual disability, and, in two out of four cases, epilepsy. None, however, displayed the central visual failure seen in PCH case subjects where other subunits of the TSEN are mutated, and only one was affected by the extensive motor defects that are typical in other forms of PCH2. The three amino acid substitutions impacted the protein level of TSEN15 and the stoichiometry of the interacting subunits in different ways, but all resulted in an almost complete loss of in vitro tRNA cleavage activity. Taken together, our results demonstrate that mutations in any known subunit of the TSEN complex can cause PCH and progressive microcephaly, emphasizing the importance of its function during brain development.},
author = {Breuss, Martin W. and Sultan, Tipu and James, Kiely N. and Rosti, Rasim O. and Scott, Eric and Musaev, Damir and Furia, Bansri and Reis, André and Sticht, Heinrich and Al-Owain, Mohammed and Alkuraya, Fowzan S. and Reuter, Miriam and Abou Jamra, Rami and Trotta, Christopher R. and Gleeson, Joseph G.},
doi = {10.1016/j.ajhg.2016.05.023},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9333},
pages = {228-35},
peerreviewed = {Yes},
title = {{Autosomal}-{Recessive} {Mutations} in the {tRNA} {Splicing} {Endonuclease} {Subunit} {TSEN15} {Cause} {Pontocerebellar} {Hypoplasia} and {Progressive} {Microcephaly}},
volume = {99},
year = {2016}
}
@article{faucris.206122158,
abstract = {PurposeTo characterize the molecular genetics of autosomal recessive Noonan syndrome.MethodsFamilies underwent phenotyping for features of Noonan syndrome in children and their parents. Two multiplex families underwent linkage analysis. Exome, genome, or multigene panel sequencing was used to identify variants. The molecular consequences of observed splice variants were evaluated by reverse-transcription polymerase chain reaction.ResultsTwelve families with a total of 23 affected children with features of Noonan syndrome were evaluated. The phenotypic range included mildly affected patients, but it was lethal in some, with cardiac disease and leukemia. All of the parents were unaffected. Linkage analysis using a recessive model supported a candidate region in chromosome 22q11, which includes LZTR1, previously shown to harbor mutations in patients with Noonan syndrome inherited in a dominant pattern. Sequencing analyses of 21 live-born patients and a stillbirth identified biallelic pathogenic variants in LZTR1, including putative loss-of-function, missense, and canonical and noncanonical splicing variants in the affected children, with heterozygous, clinically unaffected parents and heterozygous or normal genotypes in unaffected siblings.ConclusionThese clinical and genetic data confirm the existence of a form of Noonan syndrome that is inherited in an autosomal recessive pattern and identify biallelic mutations in LZTR1.Genet Med advance online publication, 22 February 2018; doi:10.1038/gim.2017.249.},
author = {Johnston, Jennifer J. and Van Der Smagt, Jasper J. and Rosenfeld, Jill A. and Pagnamenta, Alistair T. and Alswaid, Abdulrahman and Baker, Eva H. and Blair, Edward and Borck, Guntram and Brinkmann, Julia and Craigen, William and Vu Chi Dung, and Emrick, Lisa and Everman, David B. and Van Gassen, Koen L. and Gulsuner, Suleyman and Harr, Margaret H. and Jain, Mahim and Kuechler, Alma and Leppig, Kathleen A. and Mcdonald-Mcginn, Donna M. and Ngoc Thi Bich Can, and Peleg, Amir and Roeder, Elizabeth R. and Rogers, R. Curtis and Sagi-Dain, Lena and Sapp, Julie C. and Schaffer, Alejandro A. and Schanze, Denny and Stewart, Helen and Taylor, Jenny C. and Verbeek, Nienke E. and Walkiewicz, Magdalena A. and Zackai, Elaine H. and Zweier, Christiane and Zenker, Martin and Lee, Brendan and Biesecker, Leslie G.},
doi = {10.1038/gim.2017.249},
faupublication = {yes},
journal = {Genetics in Medicine},
note = {EVALuna2:34635},
peerreviewed = {Yes},
title = {{Autosomal} recessive {Noonan} syndrome associated with biallelic {LZTR1} variants},
year = {2018}
}
@article{faucris.262415947,
abstract = {Pathogenic variants in SPG11 are the most frequent cause of autosomal recessive complicated hereditary spastic paraplegia (HSP). In addition to spastic paraplegia caused by corticospinal degeneration, most patients are significantly affected by progressive weakness and muscle wasting due to alpha motor neuron (MN) degeneration. Mitochondria play a crucial role in neuronal health, and mitochondrial deficits were reported in other types of HSPs. To investigate whether mitochondrial pathology is present in SPG11, we differentiated MNs from induced pluripotent stem cells derived from SPG11 patients and controls. MN derived from human embryonic stem cells and an isogenic SPG11 knockout line were also included in the study. Morphological analysis of mitochondria in the MN soma versus neurites revealed specific alterations of mitochondrial morphology within SPG11 neurites, but not within the soma. In addition, impaired mitochondrial membrane potential was indicative of mitochondrial dysfunction. Moreover, we reveal neuritic aggregates further supporting neurite pathology in SPG11. Correspondingly, using a microfluidic-based MN culture system, we demonstrate that axonal mitochondrial transport was significantly impaired in SPG11. Overall, our data demonstrate that alterations in morphology, function, and transport of mitochondria are an important feature of axonal dysfunction in SPG11 MNs.},
author = {Güner, Fabian and Pozner, Tatyana and Krach, Florian and Prots, Iryna and Loskarn, Sandra and Schlötzer-Schrehardt, Ursula and Winkler, Jürgen and Winner, Beate and Regensburger, Martin},
doi = {10.3389/fnins.2021.680572},
faupublication = {yes},
journal = {Frontiers in Neuroscience},
keywords = {SPG11; alpha motor neuron; axonal transport; hereditary spastic paraplegia; induced pluripotent stem cells; mitochondria},
note = {CRIS-Team Scopus Importer:2021-08-06},
peerreviewed = {Yes},
title = {{Axon}-{Specific} {Mitochondrial} {Pathology} in {SPG11} {Alpha} {Motor} {Neurons}},
url = {https://www.frontiersin.org/articles/10.3389/fnins.2021.680572/full},
volume = {15},
year = {2021}
}
@article{faucris.121626604,
abstract = {Truncating ASXL3 mutations were first identified in 2013 by Bainbridge et al. as a cause of syndromic intellectual disability in four children with similar phenotypes using whole-exome sequencing. The clinical features - postulated by Bainbridge et al. to be overlapping with Bohring-Opitz syndrome - were developmental delay, severe feeding difficulties, failure to thrive and neurological abnormalities. This condition was included in OMIM as 'Bainbridge-Ropers syndrome' (BRPS, #615485). To date, a total of nine individuals with BRPS have been published in the literature in four reports (Bainbridge et al., Dinwiddie et al, Srivastava et al. and Hori et al.). In this report, we describe six unrelated patients with newly diagnosed heterozygous de novo loss-of-function variants in ASXL3 and concordant clinical features: severe muscular hypotonia with feeding difficulties in infancy, significant motor delay, profound speech impairment, intellectual disability and a characteristic craniofacial phenotype (long face, arched eyebrows with mild synophrys, downslanting palpebral fissures, prominent columella, small alae nasi, high, narrow palate and relatively little facial expression). The majority of key features characteristic for Bohring-Opitz syndrome were absent in our patients (eg, the typical posture of arms, intrauterine growth retardation, microcephaly, trigonocephaly, typical facial gestalt with nevus flammeus of the forehead and exophthalmos). Therefore we emphasize that BRPS syndrome, caused by ASXL3 loss-of-function variants, is a clinically distinct intellectual disability syndrome with a recognizable phenotype distinguishable from that of Bohring-Opitz syndrome.European Journal of Human Genetics advance online publication, 30 November 2016; doi:10.1038/ejhg.2016.165.},
author = {Kuechler, Alma and Czeschik, Johanna Christina and Graf, Elisabeth and Grasshoff, Ute and Hüffmeier, Ulrike and Busa, Tiffany and Beck-Woedl, Stefanie and Faivre, Laurence and Riviere, Jean-Baptiste and Bader, Ingrid and Koch, Johannes and Reis, André and Hehr, Ute and Rittinger, Olaf and Sperl, Wolfgang and Haack, Tobias B. and Wieland, Thomas and Engels, Hartmut and Prokisch, Holger and Strom, Tim M. and Luedecke, Hermann-Josef and Wieczorek, Dagmar},
doi = {10.1038/ejhg.2016.165},
faupublication = {yes},
journal = {European journal of human genetics},
note = {EVALuna2:9349},
peerreviewed = {Yes},
title = {{Bainbridge}-{Ropers} syndrome caused by loss-of-function variants in {ASXL3}: a recognizable condition},
year = {2016}
}
@article{faucris.267483430,
abstract = {Context: CPE encodes carboxypeptidase E, an enzyme that converts proneuropeptides and propeptide hormones to bioactive forms. It is widely expressed in the endocrine and central nervous system. To date, 4 individuals from 2 families with core clinical features including morbid obesity, neurodevelopmental delay, and hypogonadotropic hypogonadism, harboring biallelic loss-of-function (LoF) CPE variants, have been reported. Objective: We describe 4 affected individuals from 3 unrelated consanguineous families, 2 siblings of Syrian, 1 of Egyptian, and 1 of Pakistani descent, all harboring novel homozygous CPE LoF variants. Methods: After excluding Prader-Willi syndrome (PWS), exome sequencing was performed in both Syrian siblings. The variants identified in the other 2 individuals were reported as research variants in a large-scale exome study and in the ClinVar database. Computational modeling of all possible missense alterations allowed assessing CPE tolerance to missense variants. Results: All affected individuals were severely obese with neurodevelopmental delay and other endocrine anomalies. Three individuals from 2 families shared the same CPE homozygous truncating variant c.361C†>†T, p.(Arg121∗), while the fourth carried the c.994del, p.(Ser333Alafs∗22) variant. Comparison of clinical features with previously described cases and standardization according to the Human Phenotype Ontology terms indicated a recognizable clinical phenotype, which we termed Blakemore-Durmaz-Vasileiou (BDV) syndrome. Computational analysis indicated high conservation of CPE domains and intolerance to missense changes. Conclusion: Biallelic truncating CPE variants are associated with BDV syndrome, a clinically recognizable monogenic recessive syndrome with childhood-onset obesity, neurodevelopmental delay, hypogonadotropic hypogonadism, and hypothyroidism. BDV syndrome resembles PWS. Our findings suggest missense variants may also be clinically relevant. },
author = {Bosch, Elisabeth and Hebebrand, Moritz and Popp, Bernt and Penger, Theresa and Behring, Bettina and Cox, Helen and Towner, Shelley and Kraus, Cornelia and Wilson, William G. and Khan, Shagufta and Krumbiegel, Mandy and Ekici, Arif Bülent and Uebe, Steffen and Trollmann, Regina and Wölfle, Joachim and Reis, André and Vasileiou, Georgia},
doi = {10.1210/clinem/dgab592},
faupublication = {yes},
journal = {Journal of Clinical Endocrinology and Metabolism},
keywords = {BDV syndrome; carboxypeptidase E; CPE; hypogonadotropic hypogonadism; neurodevelopmental disorder; obesity},
note = {CRIS-Team Scopus Importer:2021-12-24},
pages = {3413-3427},
peerreviewed = {Yes},
title = {{BDV} {Syndrome}: {An} {Emerging} {Syndrome} with {Profound} {Obesity} and {Neurodevelopmental} {Delay} {Resembling} {Prader}-{Willi} {Syndrome}},
volume = {106},
year = {2021}
}
@article{faucris.274953208,
abstract = {Nephronophthisis-related ciliopathies (NPHP-RC) comprises a group of inherited kidney diseases, caused by mutations in genes encoding proteins localizing to primary cilia. NPHP-RC represents one of the most frequent monogenic causes of renal failure within the first three decades of life, but its molecular disease mechanisms remain unclear. Here, we identified biallelic ANKS6 mutations in two affected siblings with late-onset chronic kidney disease by whole-exome sequencing. We employed patient-derived fibroblasts generating an in vitro model to study the precise biological impact of distinct human ANKS6 mutations, completed by immunohistochemistry studies on renal biopsy samples. Functional studies using patient-derived cells showed an impaired integrity of the ciliary inversin compartment with reduced cilia length. Further analyses demonstrated that ANKS6 deficiency leads to a dysregulation of Hippo-signaling through nuclear yes-associated protein (YAP) imbalance and disrupted ciliary localization of YAP. In addition, an altered transcriptional activity of canonical Wnt target genes and altered expression of non-phosphorylated (active) beta-catenin and phosphorylated glycogen synthase kinase 3 beta were observed. Upon ciliation, ANKS6 deficiency revealed a deranged subcellular localization and expression of components of the endocytic recycling compartment. Our results demonstrate that ANKS6 plays a key role in regulating the Hippo pathway, and ANKS6 deficiency is linked to dysregulation of signaling pathways. Our study provides molecular clues in understanding pathophysiological mechanisms of NPHP-RC and may offer new therapeutic targets.},
author = {Schwarz, Hannah and Popp, Bernt and Airik, Rannar and Torabi Sarijalo, Nasrin and Knaup, Karl and Stoeckert, Johanna and Wiech, Thorsten and Amann, Kerstin Ute and Wiesmann da Silva Reis, André and Schiffer, Mario and Schueler, Markus and Wiesener, Michael},
doi = {10.1093/hmg/ddab322},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {CRIS-Team WoS Importer:2022-05-13},
peerreviewed = {Yes},
title = {{Biallelic} {ANKS6} mutations cause late-onset ciliopathy with chronic kidney disease through {YAP} dysregulation},
year = {2021}
}
@article{faucris.205109105,
abstract = {BACKGROUND: Providing the correct diagnosis for patients with tubulointerstitial kidney disease and secondary degenerative disorders, such as hypertension, remains a challenge. The autosomal dominant tubulointerstitial kidney disease (ADTKD) subtype caused by MUC1 mutations (ADTKD-MUC1) is particularly difficult to diagnose, because the mutational hotspot is a complex repeat domain, inaccessible with routine sequencing techniques. Here, we further evaluated SNaPshot minisequencing as a technique for diagnosing ADTKD-MUC1 and assessed immunodetection of the disease-associated mucin 1 frameshift protein (MUC1-fs) as a nongenetic technique.
METHODS: We re-evaluated detection of MUC1 mutations by targeted repeat enrichment and SNaPshot minisequencing by haplotype reconstruction via microsatellite analysis in three independent ADTKD-MUC1 families. Additionally, we generated rabbit polyclonal antibodies against MUC1-fs and evaluated immunodetection of wild-type and mutated allele products in human kidney biopsy specimens.
RESULTS: The detection of MUC1 mutations by SNaPshot minisequencing was robust. Immunostaining with our MUC1-fs antibodies and an MUC1 antibody showed that both proteins are readily detectable in human ADTKD-MUC1 kidneys, with mucin 1 localized to the apical membrane and MUC1-fs abundantly distributed throughout the cytoplasm. Notably, immunohistochemical analysis of MUC1-fs expression in clinical kidney samples facilitated reliable prediction of the disease status of individual patients.
CONCLUSIONS: Diagnosing ADTKD-MUC1 by molecular genetics is possible, but it is technically demanding and labor intensive. However, immunohistochemistry on kidney biopsy specimens is feasible for nongenetic diagnosis of ADTKD-MUC1 and therefore, a valid method to select families for further diagnostics. Our data are compatible with the hypothesis that specific molecular effects of MUC1-fs underlie the pathogenesis of this disease.},
author = {Knaup, Karl and Hackenbeck, Thomas and Popp, Bernt and Stoeckert, Johanna and Wenzel, Andrea and Büttner-Herold, Maike and Pfister, Frederick and Schüler, Markus and Seven, Didem and May, Annette M. and Halbritter, Jan and Gröne, Hermann Josef and Reis, André and Beck, Bodo B. and Amann, Kerstin Ute and Ekici, Arif Bülent and Wiesener, Michael S.},
doi = {10.1681/ASN.2018030245},
faupublication = {yes},
journal = {Journal of the American Society of Nephrology},
note = {EVALuna2:34428},
peerreviewed = {Yes},
title = {{Biallelic} {Expression} of {Mucin}-1 in {Autosomal} {Dominant} {Tubulointerstitial} {Kidney} {Disease}: {Implications} for {Nongenetic} {Disease} {Recognition}},
year = {2018}
}
@article{faucris.205570184,
abstract = {3MC syndrome is a rare autosomal recessive disorder with characteristic craniofacial dysmorphism and multiple anomalies. It is caused by biallelic mutations in one of three genes, MASP1, COLEC11 and COLEC10, all encoding factors of the lectin complement pathway. In MASP1, either truncating mutations or missense variants in exon 12 encoding the C-terminal serine protease domain specific for isoform MASP-3 are causative. By trio exome sequencing we now identified a novel, homozygous 2kb deletion, partially affecting exon 12 in an adult female with the typical facial gestalt of 3MC syndrome and hearing loss, but without the main feature cleft lip/palate, and without intellectual disability, or short stature. We therefore expand the MASP1 associated mutational and clinical spectrum and describe the development of her clinical presentation over a period of 21 years. As the homozygous deletion in our patient was only found by thorough and visual evaluation of the whole exome sequencing data, such deletions might escape detection in some routine diagnostic workflows and might explain a few of the so far molecularly unconfirmed cases of 3MC syndrome.},
author = {Graul-Neumann, Luitgard M. and Mensah, Martin A. and Klopocki, Eva and Uebe, Steffen and Ekici, Arif Bülent and Thiel, Christian and Reis, André and Zweier, Christiane},
doi = {10.1016/j.ejmg.2018.01.016},
faupublication = {yes},
journal = {European Journal of Medical Genetics},
note = {EVALuna2:34626},
pages = {363-368},
peerreviewed = {Yes},
title = {{Biallelic} intragenic deletion in {MASP1} in an adult female with {3MC} syndrome},
volume = {61},
year = {2018}
}
@article{faucris.112180244,
abstract = {Chromosomal microarray testing is commonly used to identify disease causing de novo copy number variants in patients with developmental delay and multiple congenital anomalies. In such a patient we now observed an 150 kb deletion on chromosome 7q21.11 affecting the first exon of the axon guidance molecule gene SEMA3A (sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3A). This deletion was inherited from the healthy father, but considering the function of SEMA3A and phenotypic similarity to the knock-out mice, we still assumed a pathogenic relevance and tested for a recessive second defect. Sequencing of SEMA3A in the patient indeed revealed the de novo in-frame mutation p.Phe316{\_}Lys317delinsThrSerSerAsnGlu. Cloning of the mutated allele in combination with two informative SNPs confirmed compound heterozygosity in the patient. While the altered protein structure was predicted to be benign, aberrant splicing resulting in a premature stop codon was proven by RT-PCR to occur in about half of the transcripts from this allele. Expression profiling in human fetal and adult cDNA panels, confirmed a high expression of SEMA3A in all brain regions as well as in adult and fetal heart and fetal skeletal muscle. Normal intellectual development in the patient was surprising but may be explained by the remaining 20% of SEMA3A expression level demonstrated by quantitative RT-PCR. We therefore report a novel autosomal recessive syndrome characterized by postnatal short stature with relative macrocephaly, camptodactyly, septal heart defect and several minor anomalies caused by biallelic mutations in SEMA3A.},
author = {Hofmann, Kristin and Zweier, Markus and Sticht, Heinrich and Zweier, Christiane and Wittmann, Wolfgang and Hoyer, Juliane and Uebe, Steffen and Van Haeringen, Arie and Thiel, Christian and Ekici, Arif Bülent and Reis, André and Rauch, Anita},
doi = {10.1002/ajmg.a.36250},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
note = {EVALuna2:9194},
pages = {2880-9},
peerreviewed = {Yes},
title = {{Biallelic} {SEMA3A} defects cause a novel type of syndromic short stature},
volume = {161A},
year = {2013}
}
@article{faucris.212339426,
abstract = {Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.
Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.
Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).
Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.
},
author = {Guo, Qi and Burgess, Stephen and Turman, Constance and Bolla, Manjeet K. and Wang, Qin and Lush, Michael and Abraham, Jean and Aittomaki, Kristiina and Andrulis, Irene L. and Apicella, Carmel and Arndt, Volker and Barrdahl, Myrto and Benitez, Javier and Berg, Christine D. and Blomqvist, Carl and Bojesen, Stig E. and Bonanni, Bernardo and Brand, Judith S. and Brenner, Hermann and Broeks, Annegien and Burwinkel, Barbara and Caldas, Carlos and Campa, Daniele and Canzian, Federico and Chang-Claude, Jenny and Chanock, Stephen J. and Chin, Suet-Feung and Couch, Fergus J. and Cox, Angela and Cross, Simon S. and Cybulski, Cezary and Czene, Kamila and Darabi, Hatef and Devilee, Peter and Diver, W. Ryan and Dunning, Alison M. and Earl, Helena M. and Eccles, Diana M. and Ekici, Arif Bülent and Eriksson, Mikael and Evans, D. Gareth and Fasching, Peter and Figueroa, Jonine and Flesch-Janys, Dieter and Flyger, Henrik and Gapstur, Susan M. and Gaudet, Mia M. and Giles, Graham G. and Glendon, Gord and Grip, Mervi and Gronwald, Jacek and Häberle, Lothar and Haiman, Christopher A. and Hall, Per and Hamann, Ute and Hankinson, Susan and Hartikainen, Jaana M. and Hein, Alexander and Hiller, Louise and Hogervorst, Frans B. and Holleczek, Bernd and Hooning, Maartje J. and Hoover, Robert N. and Humphreys, Keith and Hunter, David J. and Husing, Anika and Jakubowska, Anna and Jukkola-Vuorinen, Arja and Kaaks, Rudolf and Kabisch, Maria and Kataja, Vesa and Knight, Julia A. and Koppert, Linetta B. and Kosma, Veli-Matti and Kristensen, Vessela N. and Lambrechts, Diether and Le Marchand, Loic and Li, Jingmei and Lindblom, Annika and Lindstrom, Sara and Lissowska, Jolanta and Lubinski, Jan and Machiela, Mitchell J. and Mannermaa, Arto and Manoukian, Siranoush and Margolin, Sara and Marme, Federik and Martens, John W. M. and Mclean, Catriona and Menendez, Primitiva and Milne, Roger L. and Mulligan, Anna Marie and Muranen, Taru A. and Nevanlinna, Heli and Neven, Patrick and Nielsen, Sune F. and Nordestgaard, Borge G. and Olson, Janet E. and Perez, Jose I. A. and Peterlongo, Paolo and Phillips, Kelly-Anne and Poole, Christopher J. and Pylkas, Katri and Radice, Paolo and Rahman, Nazneen and Rudiger, Thomas and Rudolph, Anja and Sawyer, Elinor J. and Schumacher, Fredrick and Seibold, Petra and Seynaeve, Caroline and Shah, Mitul and Smeets, Ann and Southey, Melissa C. and Tollenaar, Rob A. E. M. and Tomlinson, Ian and Tsimiklis, Helen and Ulmer, Hans-Ulrich and Vachon, Celine and Van Den Ouweland, Ans M. W. and Van'T Veer, Laura J. and Wildiers, Hans and Willett, Walter and Winqvist, Robert and Zamora, M. Pilar and Chenevix-Trench, Georgia and Dork, Thilo and Easton, Douglas F. and Garcia-Closas, Montserrat and Kraft, Peter and Hopper, John L. and Zheng, Wei and Schmidt, Marjanka K. and Pharoah, Paul D. P.},
doi = {10.1093/ije/dyx131},
faupublication = {yes},
journal = {International Journal of Epidemiology},
note = {EVALuna2:33863},
pages = {1814-1822},
peerreviewed = {Yes},
title = {{Body} mass index and breast cancer survival: a {Mendelian} randomization analysis},
volume = {46},
year = {2017}
}
@article{faucris.205567447,
abstract = {PURPOSE: BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy.
METHODS: Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival.
RESULTS: Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status.
CONCLUSIONS: BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.},
author = {Wunderle, Marius and Gaß, Paul and Häberle, Lothar and Flesch, Vivien M. and Rauh, Claudia and Bani, Mayada and Hack, Carolin and Schrauder, Michael G. and Jud, Sebastian and Emons, Julius and Erber, Ramona and Ekici, Arif Bülent and Hoyer, Juliane and Vasileiou, Georgia and Kraus, Cornelia and Reis, André and Hartmann, Arndt and Lux, Michael P. and Beckmann, Matthias and Fasching, Peter and Hein, Alexander},
doi = {10.1007/s10549-018-4797-8},
faupublication = {yes},
journal = {Breast Cancer Research and Treatment},
note = {EVALuna2:34606},
pages = {85-94},
peerreviewed = {Yes},
title = {{BRCA} mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients},
volume = {171},
year = {2018}
}
@article{faucris.241258806,
abstract = {BACKGROUND: BRCA1/2 deleterious variants account for most of the hereditary breast and ovarian cancer cases. Prediction models and guidelines for the assessment of genetic risk rely heavily on criteria with high variability such as family cancer history. Here we investigated the efficacy of MRI (magnetic resonance imaging) texture features as a predictor for BRCA mutation status. METHODS: A total of 41 female breast cancer individuals at high genetic risk, sixteen with a BRCA1/2 pathogenic variant and twenty five controls were included. From each MRI 4225 computer-extracted voxels were analyzed. Non-imaging features including clinical, family cancer history variables and triple negative receptor status (TNBC) were complementarily used. Lasso-principal component regression (L-PCR) analysis was implemented to compare the predictive performance, assessed as area under the curve (AUC), when imaging features were used, and lasso logistic regression or conventional logistic regression for the remaining analyses. RESULTS: Lasso-selected imaging principal components showed the highest predictive value (AUC 0.86), surpassing family cancer history. Clinical variables comprising age at disease onset and bilateral breast cancer yielded a relatively poor AUC (~ 0.56). Combination of imaging with the non-imaging variables led to an improvement of predictive performance in all analyses, with TNBC along with the imaging components yielding the highest AUC (0.94). Replacing family history variables with imaging components yielded an improvement of classification performance of ~ 4%, suggesting that imaging compensates the predictive information arising from family cancer structure. CONCLUSIONS: The L-PCR model uncovered evidence for the utility of MRI texture features in distinguishing between BRCA1/2 positive and negative high-risk breast cancer individuals, which may suggest value to diagnostic routine. Integration of computer-extracted texture analysis from MRI modalities in prediction models and inclusion criteria might play a role in reducing false positives or missed cases especially when established risk variables such as family history are missing.},
author = {Vasileiou, Georgia and Costa, Maria J. and Long, Christopher and Wetzler, Iris and Hoyer, Juliane and Kraus, Cornelia and Popp, Bernt and Emons, Julius and Wunderle, Marius and Wenkel, Evelyn and Uder, Michael and Beckmann, Matthias and Jud, Sebastian and Fasching, Peter and Reis, André and Hammon, Matthias and Cavallaro, Alexander Josef},
doi = {10.1186/s12880-020-00483-2},
faupublication = {yes},
journal = {BMC Medical Imaging},
keywords = {BRCA1/2; Breast cancer; HBOC; L-PCR; MRI; Texture analysis},
note = {CRIS-Team Scopus Importer:2020-08-07},
pages = {86-},
peerreviewed = {unknown},
title = {{Breast} {MRI} texture analysis for prediction of {BRCA}-associated genetic risk},
volume = {20},
year = {2020}
}
@article{faucris.224746737,
abstract = {We report the case of a 3-year-old boy presenting with bilateral keratoglobus and blue sclera in addition to hallux valgus, arachnodactyly, small joint hypermobility, mitral valve dysfunction and a history of generalized muscular hypotonia in early infancy. Molecular genetics provided evidence of two pathogenic mutations in the ZNF469 gene (compound heterozygosity) leading to the diagnosis of brittle cornea syndrome type 1. In addition to neuropediatric care, spectacles were prescribed to correct refractive error and for ocular protection. Owing to the thin cornea and sclera, eye injuries are the main cause for irreversible visual loss in this disease.},
author = {Menzel-Severing, Johannes and Meiller, Ralph and Kraus, Cornelia and Trollmann, Regina and Atalay, Deniz},
doi = {10.1007/s00347-018-0796-8},
faupublication = {yes},
journal = {Ophthalmologe},
keywords = {Blue sclera; Connective tissue disease; Hereditary eye disease; Keratoglobus; Pediatric ophthalmology},
note = {CRIS-Team Scopus Importer:2019-08-20},
pages = {780-784},
peerreviewed = {Yes},
title = {{Brittle}-{Cornea}-{Syndrom} {Typ} 1 durch {Compound}-{Heterozygotie} zweier {Mutationen} im {ZNF469}-{Gen}},
volume = {116},
year = {2019}
}
@article{faucris.117320104,
abstract = {Previous findings of the Franconian Alcoholism Research Studies showed that both the CAGn of the androgen receptor (AR) and the promoter methylation of the hypothalamic peptide proopiomelanocortin (POMC) were associated with craving of male alcohol-dependent patients.Based on the strong interactions between the hypothalamic-pituitary-gonadal (HPG) and the hypothalamic-pituitary-adrenal axis (HPA), this study investigated the relationships between the CAGn repeat of the AR, POMC promoter methylation and craving of male alcohol-dependent patients.This analysis covers 84 male patients with a diagnosis of alcohol dependence (DSM-IV). We sequenced the POMC gene promoter using bisulfite modified DNA to display the methylation status. Furthermore, we sequenced the CAGn repeat within exon 1 of the AR gene. Craving was quantified by the Obsessive Compulsive Drinking Scale.We found an inverse correlation between the number of CAGn repeats of the AR and the POMC methylation status in this study. Altogether, the POMC promoter methylation accounted for 33 % of the relationship between CAGn AR polymorphism and craving.This work shows that the AR and the POMC gene might functionally interact with each other and subsequently mediate craving in alcohol-dependent patients. The paper discusses different mechanisms which might underlie our findings involving sex hormones' and sex determining region of Y-gene's regulatory function on DNA-methyltransferase activity. In conclusion, the results give insight in the interaction between HPG and HPA axis. This study is a further step on the way to a better understanding of genetic and non-genetic factors underlying craving for alcohol.},
author = {Muschler, Marc Andre Nicolas and Lenz, Bernd and Hillemacher, Thomas and Kraus, Cornelia and Kornhuber, Johannes and Frieling, Helge and Bleich, Stefan},
doi = {10.1007/s00213-013-3349-5},
faupublication = {yes},
journal = {Psychopharmacology},
note = {EVALuna2:9197},
pages = {2059-66},
peerreviewed = {Yes},
title = {{CAGn} repeat of the androgen receptor is linked to proopiomelanocortin promoter methylation-relevance for craving of male alcohol-dependent patients?},
volume = {231},
year = {2014}
}
@article{faucris.315113077,
abstract = {Calmodulin-binding transcriptional activator 1 (CAMTA1) is highly expressed in the brain and plays a role in cell cycle regulation, cell differentiation, regulation of long-term memory, and initial development, maturation, and survival of cerebellar neurons. The existence of human neurological phenotypes, including cerebellar dysfunction with variable cognitive and behavioral abnormalities (CECBA), associated with CAMTA1 variants, has further supported its role in brain functions. In this study, we phenotypically and molecularly characterize the largest cohort of individuals (n = 26) with 23 novel CAMTA1 variants (frameshift-7, nonsense-6, splicing-1, initiation codon-1, missense-5, and intragenic deletions-3) and compare the findings with all previously reported cases (total = 53). We show that the most notable phenotypic findings are developmental delay/intellectual disability, unsteady or uncoordinated gait, hypotonia, behavioral problems, and eye abnormalities. In addition, there is a high incidence of dysarthria, dysgraphia, microcephaly, gastrointestinal abnormalities, sleep difficulties, and nonspecific brain MRI findings; a few of which have been under-reported. More than one third of the variants in this cohort were inherited from an asymptomatic or mildly affected parent suggesting reduced penetrance and variable expressivity. Our cohort provides a comprehensive characterization of the spectrum of phenotypes and genotypes among individuals with CECBA and the large data will facilitate counseling and formulating management plans and surveillance recommendations for these individuals.},
author = {Al-Kateb, Hussam and Au, P. Y.Billie and Berland, Siren and Cogne, Benjamin and Demurger, Florence and Fluss, Joel and Isidor, Bertrand and Frank, L. Matthew and Varvagiannis, Konstantinos and Koolen, David A. and McDonald, Marie and Montgomery, Sarah and Moortgat, Stéphanie and Deprez, Marie and Karadurmus, Deniz and Paulsen, Julie and Reis, André and Rieger, Melissa and Vasileiou, Georgia and Willing, Marcia and Shinawi, Marwan},
doi = {10.1111/cge.14464},
faupublication = {yes},
journal = {Clinical Genetics},
keywords = {behavioral; CAMTA1; CECBA; developmental delay; gait; hypotonia; neurodevelopmental disorder; reduced penetrance; variants},
note = {CRIS-Team Scopus Importer:2023-12-15},
peerreviewed = {Yes},
title = {{CAMTA1}-related disorder: {Phenotypic} and molecular characterization of 26 new individuals and literature review},
year = {2023}
}
@article{faucris.309436209,
abstract = {Background: Patients with systemic lupus erythematosus (SLE), an autoimmune disease, have a higher risk of cardiovascular (CV) disease and death. In addition, up to 40%–50% of SLE patients develop lupus nephritis (LN) and chronic kidney disease, which is an additional CV risk factor. Thus, the individual contributions of LN and other SLE-specific factors to CV events are unclear. Methods: In this study, we investigated the effect of LN on the development of CV changes using the female NZBxNZW F1 (NZB/W) mouse model of lupus-like disease, with female NZW mice as controls. Standard serologic, morphologic, immunohistologic, and molecular analyses were performed. In a separate group of NZB/W mice, systolic blood pressure (BP) was measured during the course of the disease using tail plethysmography. Results: Our data show marked CV changes in NZB/W mice, i.e., increased heart weight, hypertrophy of the left ventricle (LV) and septum, and increased wall thickness of the intramyocardial arteries and the aorta, which correlated with the progression of renal damage, but not with the age of the mice. In addition, systolic BP was increased in NZB/W mice only when kidney damage progressed and proteinuria was present. Pathway analysis based on gene expression data revealed a significant upregulation of the response to interferon beta in NZB/W mice with moderate kidney injury compared with NZB mice. Furthermore, IFI202b and IL-6 mRNA expression is correlated with CV changes. Multiple linear regression analysis demonstrated serum urea as a surrogate marker of kidney function and IFI202b expression as an independent predictor for LV wall thickness. In addition, deposition of complement factors CFD and C3c in hearts from NZB/W mice was seen, which correlated with the severity of kidney disease. Conclusions: Thus, we postulate that the pathogenesis of CV disease in SLE is affected by renal impairment, i.e., LN, but it can also be partly influenced by lupus-specific cardiac expression of pro-inflammatory factors and complement deposition.},
author = {Böhme, Romy and Daniel, Christoph and Ferrazzi, Fulvia and Angeloni, Miriam and Ekici, Arif Bülent and Winkler, Thomas and Hilgers, Karl Friedrich and Wellmann, Ute and Voll, Reinhard E. and Amann, Kerstin Ute},
doi = {10.3389/fcvm.2023.1182193},
faupublication = {yes},
journal = {Frontiers in Cardiovascular Medicine},
keywords = {autoimmune disease; cardiovascular disease; IL-15; interferon-related; renal disease; systemic lupus erythematosus},
note = {CRIS-Team Scopus Importer:2023-08-18},
peerreviewed = {Yes},
title = {{Cardiovascular} changes in the {NZB}/{W} {F1} mouse model of lupus nephritis},
volume = {10},
year = {2023}
}
@article{faucris.123459864,
abstract = {Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare disorder caused by mutations in the PHF6 gene. It manifests as syndromic X-linked recessive intellectual disability (ID) in males and as sporadic ID due to de novo mutations in females. Clinical features include variable ID and a range of somatic manifestations constituting a distinct phenotype in both males and females, respectively, including seizures in a few. Central nervous system (CNS) imaging data are largely unavailable for BFLS. Here we report on CNS MRI findings from two female individuals with BFLS due to a de novo duplication in PHF6 who presented with typical BFLS and epilepsy. Brain findings encompass an intriguing combination of structural abnormalities including a simplified gyral pattern and aspects resembling subcortical band heterotopia as signs of malformation of cortical development (MCD). This finding is of note, since PHF6 has been suggested to play pivotal roles in CNS development including neuronal migration.},
author = {Kasper, Burkhard and Dörfler, Arnd and Di Donato, Nataliya and Kasper, Ekkehard M. and Wieczorek, Dagmar and Hoyer, Juliane and Zweier, Christiane},
doi = {10.1016/j.yebeh.2017.01.022},
faupublication = {yes},
journal = {Epilepsy and Behavior},
note = {EVALuna2:9368},
pages = {104-109},
peerreviewed = {Yes},
title = {{Central} nervous system anomalies in two females with {Borjeson}-{Forssman}-{Lehmann} syndrome},
volume = {69},
year = {2017}
}
@article{faucris.204650253,
abstract = {Spermatogenesis in the mouse has been extensively studied for decades. Previous methods, such as histological staining or bulk transcriptome analysis, either lacked resolution at the single-cell level or were focused on a very narrowly defined set of factors. Here, we present the first comprehensive, unbiased single-cell transcriptomic view of mouse spermatogenesis. Our single-cell RNA-seq (scRNA-seq) data on over 2,500 cells from the mouse testis improves upon stage marker detection and validation, capturing the continuity of differentiation rather than artificially chosen stages. scRNA-seq also enables the analysis of rare cell populations masked in bulk sequencing data and reveals new insights into the regulation of sex chromosomes during spermatogenesis. Our data provide the basis for further studies in the field, for the first time providing a high-resolution reference of transcriptional processes during mouse spermatogenesis.
},
author = {Lukassen, Sören and Bosch, Elisabeth and Ekici, Arif Bülent and Winterpacht, Andreas},
doi = {10.1038/s41598-018-24725-0},
faupublication = {yes},
journal = {Scientific Reports},
note = {EVALuna2:34135},
peerreviewed = {Yes},
title = {{Characterization} of germ cell differentiation in the male mouse through single-cell {RNA} sequencing},
volume = {8},
year = {2018}
}
@article{faucris.208411267,
abstract = {Chromatin remodeling is of crucial importance during brain development. Pathogenic alterations of several chromatin remodeling ATPases have been implicated in neurodevelopmental disorders. We describe an index case with a de novo missense mutation in CHD3, identified during whole genome sequencing of a cohort of children with rare speech disorders. To gain a comprehensive view of features associated with disruption of this gene, we use a genotype-driven approach, collecting and characterizing 35 individuals with de novo CHD3 mutations and overlapping phenotypes. Most mutations cluster within the ATPase/helicase domain of the encoded protein. Modeling their impact on the three-dimensional structure demonstrates disturbance of critical binding and interaction motifs. Experimental assays with six of the identified mutations show that a subset directly affects ATPase activity, and all but one yield alterations in chromatin remodeling. We implicate de novo CHD3 mutations in a syndrome characterized by intellectual disability, macrocephaly, and impaired speech and language.},
author = {Blok, Lot Snijders and Rousseau, Justine and Twist, Joanna and Ehresmann, Sophie and Takaku, Motoki and Venselaar, Hanka and Rodan, Lance H. and Nowak, Catherine B. and Douglas, Jessica and Swoboda, Kathryn J. and Steeves, Marcie A. and Sahai, Inderneel and Stumpel, Connie T. R. M. and Stegmann, Alexander P. A. and Wheeler, Patricia and Willing, Marcia and Fiala, Elise and Kochhar, Aaina and Gibson, William T. and Cohen, Ana S. A. and Agbahovbe, Ruky and Innes, A. Micheil and Au, P. Y. Billie and Rankin, Julia and Anderson, Ilse J. and Skinner, Steven A. and Louie, Raymond J. and Warren, Hannah E. and Afenjar, Alexandra and Keren, Boris and Nava, Caroline and Buratti, Julien and Isapof, Arnaud and Rodriguez, Diana and Lewandowski, Raymond and Propst, Jennifer and Van Essen, Ton and Choi, Murim and Lee, Sangmoon and Chae, Jong H. and Price, Susan and Schnur, Rhonda E. and Douglas, Ganka and Wentzensen, Ingrid M. and Zweier, Christiane and Reis, André and Bialer, Martin G. and Moore, Christine and Koopmans, Marije and Brilstra, Eva H. and Monroe, Glen R. and Van Gassen, Koen L. and Van Binsbergen, Ellen and Newbury-Ecob, Ruth and Bownass, Lucy and Bader, Ingrid and Mayr, Johannes A. and Wortmann, Saskia B. and Jakielski, Kathy J. and Strand, Edythe A. and Kloth, Katja and Bierhals, Tatjana and Roberts, John D. and Petrovich, Robert M. and Machida, Shinichi and Kurumizaka, Hitoshi and Lelieveld, Stefan and Pfundt, Rolph and Jansen, Sandra and Deriziotis, Pelagia and Faive, Laurence and Thevenon, Julien and Assoum, Mirna and Shriberg, Lawrence and Kleefstra, Tjitske and Brunner, Han G. and Wade, Paul A. and Fisher, Simon E. and Campeau, Philippe M.},
doi = {10.1038/s41467-018-06014-6},
faupublication = {yes},
journal = {Nature Communications},
note = {EVALuna2:34823},
peerreviewed = {Yes},
title = {{CHD3} helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language},
volume = {9},
year = {2018}
}
@article{faucris.230818545,
author = {Blok, Lot Snijders and Rousseau, Justine and Twist, Joanna and Ehresmann, Sophie and Takaku, Motoki and Venselaar, Hanka and Rodan, Lance H. and Nowak, Catherine B. and Douglas, Jessica and Swoboda, Kathryn J. and Steeves, Marcie A. and Sahai, Inderneel and Stumpel, Connie T. R. M. and Stegmann, Alexander P. A. and Wheeler, Patricia and Willing, Marcia and Fiala, Elise and Kochhar, Aaina and Gibson, William T. and Cohen, Ana S. A. and Agbahovbe, Ruky and Innes, A. Micheil and Au, P. Y. Billie and Rankin, Julia and Anderson, Ilse J. and Skinner, Steven A. and Louie, Raymond J. and Warren, Hannah E. and Afenjar, Alexandra and Keren, Boris and Nava, Caroline and Buratti, Julien and Isapof, Arnaud and Rodriguez, Diana and Lewandowski, Raymond and Propst, Jennifer and Van Essen, Ton and Choi, Murim and Lee, Sangmoon and Chae, Jong H. and Price, Susan and Schnur, Rhonda E. and Douglas, Ganka and Wentzensen, Ingrid M. and Zweier, Christiane and Reis, André and Bialer, Martin G. and Moore, Christine and Koopmans, Marije and Brilstra, Eva H. and Monroe, Glen R. and Van Gassen, Koen L. I. and Van Binsbergen, Ellen and Newbury-Ecob, Ruth and Bownass, Lucy and Bader, Ingrid and Mayr, Johannes A. and Wortmann, Saskia B. and Jakielski, Kathy J. and Strand, Edythe A. and Kloth, Katja and Bierhals, Tatjana and Roberts, John D. and Petrovich, Robert M. and Machida, Shinichi and Kurumizaka, Hitoshi and Lelieveld, Stefan and Pfundt, Rolph and Jansen, Sandra and Deriziotis, Pelagia and Faivre, Laurence and Thevenon, Julien and Assoum, Mirna and Shriberg, Lawrence and Kleefstra, Tjitske and Brunner, Han G. and Wade, Paul A. and Fisher, Simon E. and Campeau, Philippe M. and Mcrae, Jeremy F. and Clayton, Stephen and Fitzgerald, Tomas W. and Kaplanis, Joanna and Prigmore, Elena and Rajan, Diana and Sifrim, Alejandro and Aitken, Stuart and Akawi, Nadia and Alvi, Mohsan and Ambridge, Kirsty and Barrett, Daniel M. and Bayzetinova, Tanya and Jones, Philip and Jones, Wendy D. and King, Daniel and Krishnappa, Netravathi and Mason, Laura E. and Singh, Tarjinder and Tivey, Adrian R. and Ahmed, Munaza and Anjum, Uruj and Archer, Hayley and Armstrong, Ruth and Awada, Jana and Balasubramanian, Meena and Banka, Siddharth and Baralle, Diana and Barnicoat, Angela and Batstone, Paul and Baty, David and Bennett, Chris and Berg, Jonathan and Bernhard, Birgitta and Bevan, A. Paul and Bitner-Glindzicz, Maria and Blair, Edward and Blyth, Moira and Bohanna, David and Bourdon, Louise and Bourn, David and Bradley, Lisa and Brady, Angela and Brent, Simon and Brewer, Carole and Brunstrom, Kate and Bunyan, David J. and Burn, John and Canham, Natalie and Castle, Bruce and Chandler, Kate and Chatzimichali, Elena and Cilliers, Deirdre and Clarke, Angus and Clasper, Susan and Clayton-Smith, Jill and Clowes, Virginia and Coates, Andrea and Cole, Trevor and Colgiu, Irina and Collins, Amanda and Collinson, Morag N. and Connell, Fiona and Cooper, Nicola and Cox, Helen and Cresswell, Lara and Cross, Gareth and Crow, Yanick and D'Alessandro, Mariella and Dabir, Tabib and Davidson, Rosemarie and Davies, Sally and De Vries, Dylan and Dean, John and Deshpande, Charu and Devlin, Gemma and Dixit, Abhijit and Dobbie, Angus and Donaldson, Alan and Donnai, Dian and Donnelly, Deirdre and Donnelly, Carina and Douglas, Angela and Douzgou, Sofia and Duncan, Alexis and Eason, Jacqueline and Ellard, Sian and Ellis, Ian and Elmslie, Frances and Evans, Karenza and Everest, Sarah and Fendick, Tina and Fisher, Richard and Flinter, Frances and Foulds, Nicola and Fry, Andrew and Fryer, Alan and Gardiner, Carol and Gaunt, Lorraine and Ghali, Neeti and Gibbons, Richard and Gill, Harinder and Goodship, Judith and Goudie, David and Gray, Emma and Green, Andrew and Greene, Philip and Greenhalgh, Lynn and Gribble, Susan and Harrison, Rachel and Harrison, Lucy and Harrison, Victoria and Hawkins, Rose and He, Liu and Hellens, Stephen and Henderson, Alex and Hewitt, Sarah and Hildyard, Lucy and Hobson, Emma and Holden, Simon and Holder, Muriel and Holder, Susan and Hollingsworth, Georgina and Homfray, Tessa and Humphreys, Mervyn and Hurst, Jane and Hutton, Ben and Ingram, Stuart and Irving, Melita and Islam, Lily and Jackson, Andrew and Jarvis, Joanna and Jenkins, Lucy and Johnson, Diana and Jones, Elizabeth and Josifova, Dragana and Joss, Shelagh and Kaemba, Beckie and Kazembe, Sandra and Kelsell, Rosemary and Kerr, Bronwyn and Kingston, Helen and Kini, Usha and Kinning, Esther and Kirby, Gail and Kirk, Claire and Kivuva, Emma and Kraus, Alison and Kumar, Dhavendra and Kumar, V. K. Ajith and Lachlan, Katherine and Lam, Wayne and Lampe, Anne and Langman, Caroline and Lees, Melissa and Lim, Derek and Longman, Cheryl and Lowther, Gordon and Lynch, Sally A. and Magee, Alex and Maher, Eddy and Male, Alison and Mansour, Sahar and Marks, Karen and Martin, Katherine and Maye, Una and Mccann, Emma and Mcconnell, Vivienne and Mcentagart, Meriel and Mcgowan, Ruth and Mckay, Kirsten and Mckee, Shane and Mcmullan, Dominic J. and Mcnerlan, Susan and Mcwilliam, Catherine and Mehta, Sarju and Metcalfe, Kay and Middleton, Anna and Miedzybrodzka, Zosia and Miles, Emma and Mohammed, Shehla and Montgomery, Tara and Moore, David and Morgan, Sian and Morton, Jenny and Mugalaasi, Hood and Murday, Victoria and Murphy, Helen and Naik, Swati and Nemeth, Andrea and Nevitt, Louise and Norman, Andrew and O'Shea, Rosie and Ogilvie, Caroline and Ong, Kai-Ren and Park, Soo-Mi and Parker, Michael J. and Patel, Chirag and Paterson, Joan and Payne, Stewart and Perrett, Daniel and Phipps, Julie and Pilz, Daniela T. and Pollard, Martin and Pottinger, Caroline and Poulton, Joanna and Pratt, Norman and Prescott, Katrina and Pridham, Abigail and Procter, Annie and Purnell, Hellen and Quarrell, Oliver and Ragge, Nicola and Rahbari, Raheleh and Randall, Josh and Raymond, Lucy and Rice, Debbie and Robert, Leema and Roberts, Eileen and Roberts, Jonathan and Roberts, Paul and Roberts, Gillian and Ross, Alison and Rosser, Elisabeth and Saggar, Anand and Samant, Shalaka and Sampson, Julian and Sandford, Richard and Sarkar, Ajoy and Schweiger, Susann and Scott, Richard and Scurr, Ingrid and Selby, Ann and Seller, Anneke and Sequeira, Cheryl and Shannon, Nora and Sharif, Saba and Shaw-Smith, Charles and Shearing, Emma and Shears, Debbie and Sheridan, Eamonn and Simonic, Ingrid and Singzon, Roldan and Skitt, Zara and Smith, Audrey and Smith, Kath and Smithson, Sarah and Sneddon, Linda and Splitt, Miranda and Squires, Miranda and Stewart, Fiona and Stewart, Helen and Straub, Volker and Suri, Mohnish and Sutton, Vivienne and Swaminathan, Ganesh Jawahar and Sweeney, Elizabeth and Tatton-Brown, Kate and Taylor, Cat and Taylor, Rohan and Tein, Mark and Temple, I. Karen and Thomson, Jenny and Tischkowitz, Marc and Tomkins, Susan and Torokwa, Audrey and Treacy, Becky and Turner, Claire and Turnpenny, Peter and Tysoe, Carolyn and Vandersteen, Anthony and Varghese, Vinod and Vasudevan, Pradeep and Vijayarangakannan, Parthiban and Vogt, Julie and Wakeling, Emma and Wallwark, Sarah and Waters, Jonathon and Weber, Astrid and Wellesley, Diana and Whiteford, Margo and Widaa, Sara and Wilcox, Sarah and Wilkinson, Emily and Williams, Denise and Williams, Nicola and Wilson, Louise and Woods, Geoff and Wragg, Christopher and Wright, Michael and Yates, Laura and Yau, Michael and Nellaker, Chris and Parker, Michael and Firth, Helen V. and Wright, Caroline F. and Fitzpatrick, David R. and Barrett, Jeffrey C. and Hurles, Matthew E.},
doi = {10.1038/s41467-019-10161-9},
faupublication = {yes},
journal = {Nature Communications},
note = {EVALuna2:206977},
peerreviewed = {No},
title = {{CHD3} helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language (vol 9, 4619, 2018)},
volume = {10},
year = {2019}
}
@article{faucris.109616364,
abstract = {The link of chromatin remodeling to both neurodevelopment and cancer has recently been highlighted by the identification of mutations affecting BAF chromatin-remodeling components, such as ARID1B, in individuals with intellectual disability and cancer. However, the underlying molecular mechanism(s) remains unknown. Here, we show that ARID1B is a repressor of Wnt/?-catenin signaling. Through whole-transcriptome analysis, we find that in individuals with intellectual disability and ARID1B loss-of-function mutations, Wnt/?-catenin target genes are upregulated. Using cellular models of low and high Wnt/?-catenin activity, we demonstrate that knockdown of ARID1B activates Wnt/?-catenin target genes and Wnt/?-catenin-dependent transcriptional reporters in a ?-catenin-dependent manner. Reciprocally, forced expression of ARID1B inhibits Wnt/?-catenin signaling downstream of the ?-catenin destruction complex. Both endogenous and exogenous ARID1B associate with ?-catenin and repress Wnt/?-catenin-mediated transcription through the BAF core subunit BRG1. Accordingly, mutations in ARID1B leading to partial or complete deletion of its BRG1-binding domain, as is often observed in intellectual disability and cancers, compromise association with ?-catenin, and the resultant ARID1B mutant proteins fail to suppress Wnt/?-catenin signaling. Finally, knockdown of ARID1B in mouse neuroblastoma cells leads to neurite outgrowth through ?-catenin. The data suggest that aberrations in chromatin-remodeling factors, such as ARID1B, might contribute to neurodevelopmental abnormalities and cancer through deregulation of developmental and oncogenic pathways, such as the Wnt/?-catenin signaling pathway.},
author = {Vasileiou, Georgia and Ekici, Arif Bülent and Urebe, Steffen and Zweier, Christiane and Hoyer, Juliane and Engels, Hartmut and Behrens, Jürgen and Reis, André and Hadjihannas, Michel},
doi = {10.1016/j.ajhg.2015.08.002},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9258},
pages = {445-56},
peerreviewed = {Yes},
title = {{Chromatin}-{Remodeling}-{Factor} {ARID1B} {Represses} {Wnt}/?-{Catenin} {Signaling}},
volume = {97},
year = {2015}
}
@article{faucris.208381128,
abstract = {The cellular protein SPOC1 (survival time-associated PHD [plant homeodomain] finger protein in ovarian cancer 1) acts as a regulator of chromatin structure and the DNA damage response. It binds H3K4me2/3-containing chromatin and promotes DNA condensation by recruiting corepressors such as KAP-1 and H3K9 methyltransferases. Previous studies identified SPOC1 as a restriction factor against human adenovirus (HAdV) infection that is antagonized by E1B-55K/E4-orf6-dependent proteasomal degradation. Here, we demonstrate that, in contrast to HAdV-infected cells, SPOC1 is transiently upregulated during the early phase of human cytomegalovirus (HCMV) replication. We show that the expression of immediate early protein 1 (IE1) is sufficient and necessary to induce SPOC1. Additionally, we discovered that during later stages of infection, SPOC1 is downregulated in a glycogen synthase kinase 3β (GSK-3β)-dependent manner. We provide evidence that SPOC1 overexpression severely impairs HCMV replication by repressing the initiation of viral immediate early (IE) gene expression. Consistently, we observed that SPOC1-depleted primary human fibroblasts displayed an augmented initiation of viral IE gene expression. This occurs in a multiplicity of infection (MOI)-dependent manner, a defining hallmark of intrinsic immunity. Interestingly, repression requires the presence of high SPOC1 levels at the start of infection, while later upregulation had no negative impact, suggesting distinct temporal roles of SPOC1 during the HCMV replicative cycle. Mechanistically, we observed a highly specific association of SPOC1 with the major immediate early promoter (MIEP), strongly suggesting that SPOC1 inhibits HCMV replication by MIEP binding and the subsequent recruitment of heterochromatin-building factors. Thus, our data add SPOC1 as a novel factor to the endowment of a host cell to restrict cytomegalovirus infections.IMPORTANCE Accumulating evidence indicates that during millennia of coevolution, host cells have developed a sophisticated compilation of cellular factors to restrict cytomegalovirus infections. Defining this equipment is important to understand cellular barriers against viral infection and to develop strategies to utilize these factors for antiviral approaches. So far, constituents of PML nuclear bodies and interferon gamma-inducible protein 16 (IFI16) were known to mediate intrinsic immunity against HCMV. In this study, we identify the chromatin modulator SPOC1 as a novel restriction factor against HCMV. We show that preexisting high SPOC1 protein levels mediate a silencing of HCMV gene expression via a specific association with an important viral cis-regulatory element, the major immediate early promoter. Since SPOC1 expression varies between cell types, this factor may play an important role in tissue-specific defense against HCMV.
},
author = {Reichel, Anna and Stilp, Anne-Charlotte and Scherer, Myriam and Reuter, Nina and Lukassen, Sören and Kasmapour, Bahram and Schreiner, Sabrina and Cicin-Sain, Luka and Winterpacht, Andreas and Stamminger, Thomas},
doi = {10.1128/JVI.00342-18},
faupublication = {yes},
journal = {Journal of Virology},
note = {EVALuna2:34842},
peerreviewed = {Yes},
title = {{Chromatin}-{Remodeling} {Factor} {SPOC1} {Acts} as a {Cellular} {Restriction} {Factor} against {Human} {Cytomegalovirus} by {Repressing} the {Major} {Immediate} {Early} {Promoter}},
volume = {92},
year = {2018}
}
@article{faucris.252894564,
author = {Winner, Beate and Winkler, Jürgen and Uyanik, Goekhan and Cirak, Sebahattin and Hehr, Ute and et al.},
author_hint = {Olmez A, Uyanik G, Ozgul RK, Gross C, Cirak S, Elibol B, Anlar B, Winner B, Hehr U, Topaloglu H, Winkler J},
doi = {10.1055/s-2006-923982},
faupublication = {no},
journal = {Neuromuscular Disorders},
pages = {S63-S63},
peerreviewed = {Yes},
support_note = {Author relations incomplete. You may find additional data in field 'author{\_}hint'},
title = {{Clinical} and genetic characterization of {SPG11}: {Hereditary} {Spastic} {Paraplegia} with thin corpus callosum},
volume = {16},
year = {2006}
}
@article{faucris.252992822,
author = {Schuhmann, Sarah and Koller, Heiko and Sticht, Heinrich and Kraus, Cornelia and Krumbiegel, Mandy and Uebe, Steffen and Ekici, Arif Bülent and Reis, André and Thiel, Christian},
doi = {10.1111/cge.13952},
faupublication = {yes},
journal = {Clinical Genetics},
note = {CRIS-Team Scopus Importer:2021-03-26},
peerreviewed = {Yes},
title = {{Clinical} and molecular delineation of spondylocostal dysostosis type 3},
year = {2021}
}
@article{faucris.241743283,
abstract = {De novo pathogenic variants in the GATAD2B gene have been associated with a syndromic neurodevelopmental disorder (GAND) characterized by severe intellectual disability (ID), impaired speech, childhood hypotonia, and dysmorphic features. Since its first description in 2013, nine patients have been reported in case reports and a series of 50 patients was recently published, which is consistent with the relative frequency of GATAD2B pathogenic variants in public databases. We report the detailed phenotype of 19 patients from various ethnic backgrounds with confirmed pathogenic GATAD2B variants including intragenic deletions. All individuals presented developmental delay with a median age of 2.5 years for independent walking and of 3 years for first spoken words. GATAD2B variant carriers showed very little subsequent speech progress, two patients over 30 years of age remaining non-verbal. ID was mostly moderate to severe, with one profound and one mild case, which shows a wider spectrum of disease severity than previously reported. We confirm macrocephaly as a major feature in GAND (53%). Most common dysmorphic features included broad forehead, deeply set eyes, hypertelorism, wide nasal base, and pointed chin. Conversely, prenatal abnormalities, non-cerebral malformations, epilepsy, and autistic behavior were uncommon. Other features included feeding difficulties, behavioral abnormalities, and unspecific abnormalities on brain MRI. Improving our knowledge of the clinical phenotype is essential for correct interpretation of the molecular results and accurate patient management.},
author = {Vera, Gabriella and Sorlin, Arthur and Delplancq, Geoffroy and Lecoquierre, François and Brasseur-Daudruy, Marie and Petit, Florence and Smol, Thomas and Ziegler, Alban and Bonneau, Dominique and Colin, Estelle and Mercier, Sandra and Cogné, Benjamin and Bézieau, Stéphane and Edery, Patrick and Lesca, Gaetan and Chatron, Nicolas and Sabatier, Isabelle and Duban-Bedu, Bénédicte and Colson, Cindy and Piton, Amélie and Durand, Benjamin and Capri, Yline and Perrin, Laurence and Wiesener, Antje and Zweier, Christiane and Maroofian, Reza and Carroll, Christopher J. and Galehdari, Hamid and Mazaheri, Neda and Callewaert, Bert and Giulianno, Fabienne and Zaafrane-Khachnaoui, Khaoula and Buchert-Lo, Rebecca and Haack, Tobias and Magg, Janine and Rieß, Angelika and Blandfort, Maria and Waldmüller, Stephan and Horber, Veronka and Leonardi, Emanuela and Polli, Roberta and Turolla, Licia and Murgia, Alessandra and Frebourg, Thierry and Lebre, Anne Sophie and Nicolas, Gaël and Saugier-Veber, Pascale and Guerrot, Anne Marie},
doi = {10.1016/j.ejmg.2020.104004},
faupublication = {yes},
journal = {European Journal of Medical Genetics},
keywords = {Developmental delay; GATAD2B; Intellectual disability; Next-generation sequencing},
note = {CRIS-Team Scopus Importer:2020-08-21},
peerreviewed = {Yes},
title = {{Clinical} and molecular description of 19 patients with {GATAD2B}-{Associated} {Neurodevelopmental} {Disorder} ({GAND})},
volume = {63},
year = {2020}
}
@article{faucris.111090584,
abstract = {We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual "wavy" profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases.},
author = {Schuurs-Hoeijmakers, Janneke H. M. and Landsverk, Megan L. and Foulds, Nicola and Kukolich, Mary K. and Gavrilova, Ralitza H. and Greville-Heygate, Stephanie and Hanson-Kahn, Andrea and Bernstein, Jonathan A. and Glass, Jennifer and Chitayat, David and Burrow, Thomas A. and Husami, Ammar and Collins, Kathleen and Wusik, Katie and Van Der Aa, Nathalie and Kooy, Frank and Brown, Kate Tatton and Gadzicki, Dorothea and Kini, Usha and Alvarez, Sara and Fernandez-Jaen, Alberto and Mcgehee, Frank and Selby, Katherine and Tarailo-Graovac, Maja and Van Allen, Margot and Van Karnebeek, Clara D. M. and Stavropoulos, Dimitri J. and Marshall, Christian R. and Merico, Daniele and Gregor, Anne and Zweier, Christiane and Hopkin, Robert J. and Chu, Yoyo Wing-Yiu and Chung, Brian Hon-Yin and De Vries, Bert B. A. and Devriendt, Koenraad and Hurles, Matthew E. and Brunner, Han G.},
doi = {10.1002/ajmg.a.37476},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
note = {EVALuna2:9319},
pages = {670-5},
peerreviewed = {Yes},
title = {{Clinical} delineation of the {PACS1}-related syndrome - {Report} on 19 patients},
volume = {170},
year = {2016}
}
@article{faucris.205568372,
abstract = {PurposeShort stature is a common condition of great concern to patients and their families. Mostly genetic in origin, the underlying cause often remains elusive due to clinical and genetic heterogeneity.MethodsWe systematically phenotyped 565 patients where common nongenetic causes of short stature were excluded, selected 200 representative patients for whole-exome sequencing, and analyzed the identified variants for pathogenicity and the affected genes regarding their functional relevance for growth.ResultsBy standard targeted diagnostic and phenotype assessment, we identified a known disease cause in only 13.6% of the 565 patients. Whole-exome sequencing in 200 patients identified additional mutations in known short-stature genes in 16.5% of these patients who manifested only part of the symptomatology. In 15.5% of the 200 patients our findings were of significant clinical relevance. Heterozygous carriers of recessive skeletal dysplasia alleles represented 3.5% of the cases.ConclusionA combined approach of systematic phenotyping, targeted genetic testing, and whole-exome sequencing allows the identification of the underlying cause of short stature in at least 33% of cases, enabling physicians to improve diagnosis, treatment, and genetic counseling. Exome sequencing significantly increases the diagnostic yield and consequently care in patients with short stature.},
author = {Hauer, Nadine and Popp, Bernt and Schoeller, Eva and Schuhmann, Sarah and Heath, Karen E. and Hisado-Oliva, Alfonso and Klinger, Patricia and Kraus, Cornelia and Trautmann, Udo and Zenker, Martin and Zweier, Christiane and Wiesener, Antje and Abou Jamra, Rami and Kunstmann, Erdmute and Wieczorek, Dagmar and Uebe, Steffen and Ferrazzi, Fulvia and Büttner, Christian and Ekici, Arif Bülent and Rauch, Anita and Sticht, Heinrich and Dörr, Helmuth-Günther and Reis, André and Thiel, Christian},
doi = {10.1038/gim.2017.159},
faupublication = {yes},
journal = {Genetics in Medicine},
note = {EVALuna2:34628},
pages = {630-638},
peerreviewed = {Yes},
title = {{Clinical} relevance of systematic phenotyping and exome sequencing in patients with short stature},
volume = {20},
year = {2018}
}
@article{faucris.107523504,
abstract = {Segmental Xp22.2 monosomy or a heterozygous HCCS mutation is associated with the microphthalmia with linear skin defects (MLS) or MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome, an X-linked disorder with male lethality. HCCS encodes the holocytochrome c-type synthase involved in mitochondrial oxidative phosphorylation (OXPHOS) and programmed cell death.We characterized the X-chromosomal abnormality encompassing HCCS or an intragenic mutation in this gene in six new female patients with an MLS phenotype by cytogenetic analysis, fluorescence in situ hybridization, sequencing, and quantitative real-time PCR. The X chromosome inactivation (XCI) pattern was determined and clinical data of the patients were reviewed.Two terminal Xp deletions of >= 11.2 Mb, two submicroscopic copy number losses, one of ~850 kb and one of >= 3 Mb, all covering HCCS, 1 nonsense, and one mosaic 2-bp deletion in HCCS are reported. All females had a completely (>98:2) or slightly skewed (82:18) XCI pattern. The most consistent clinical features were microphthalmia/anophthalmia and sclerocornea/corneal opacity in all patients and congenital linear skin defects in 4/6. Additional manifestations included various ocular anomalies, cardiac defects, brain imaging abnormalities, microcephaly, postnatal growth retardation, and facial dysmorphism. However, no obvious clinical sign was observed in three female carriers who were relatives of one patient.Our findings showed a wide phenotypic spectrum ranging from asymptomatic females with an HCCS mutation to patients with a neonatal lethal MLS form. Somatic mosaicism and the different ability of embryonic cells to cope with an OXPHOS defect and/or enhanced cell death upon HCCS deficiency likely underlie the great variability in phenotypes.},
author = {Van Rahden, Vanessa A. and Rau, Isabella and Fuchs, Sigrid and Kosyna, Friederike K. and De Almeida, Hiram Larangeira and Fryssira, Helen and Isidor, Bertrand and Jauch, Anna and Joubert, Madeleine and Lachmeijer, Augusta M. A. and Zweier, Christiane and Moog, Ute and Kutsche, Kerstin},
doi = {10.1186/1750-1172-9-53},
faupublication = {yes},
journal = {Orphanet Journal of Rare Diseases},
note = {EVALuna2:9233},
pages = {53},
peerreviewed = {Yes},
title = {{Clinical} spectrum of females with {HCCS} mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects ({MLS}) syndrome},
volume = {9},
year = {2014}
}
@article{faucris.212302743,
abstract = {Hematotoxicity is one of the major side effects of chemotherapy. The aim of this study was to examine the association between single nucleotide polymorphisms (SNPs) and hematotoxicity in breast cancer patients in a subset of patients of the SUCCESS prospective phase III chemotherapy study. All patients (n = 1678) received three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by three cycles of docetaxel or docetaxel/gemcitabine, depending on randomization. Germline DNA was genotyped for 246 SNPs selected from a previous genome-wide association study (GWAS) in a panel of lymphoblastoid cell lines, with gemcitabine toxicity as the phenotype. All SNPs were tested for their value in predicting grade 3 or 4 neutropenic or leukopenic events (NLEs). Their prognostic value in relation to overall survival and disease-free survival was also tested. None of the SNPs was found to be predictive for NLEs during treatment with docetaxel/gemcitabine. Two SNPs in and close to the PIGB gene significantly improved the prediction of NLEs after FEC, in addition to the factors of age and body surface area. The top SNP (rs12050587) had an odds ratio of 1.38 per minor allele (95% confidence interval, 1.17 to 1.62). No associations were identified for predicting disease-free or overall survival. Genetic variance in the PIGB gene may play a role in determining interindividual differences in relation to hematotoxicity after FEC chemotherapy.},
author = {Fasching, Peter and Häberle, Lothar and Rack, Brigitte and Li, Liang and Hein, Alexander and Ekici, Arif Bülent and Reis, André and Lux, Michael P. and Cunningham, Julie M. and Rübner, Matthias and Jenkins, Gergory and Fridley, Brooke and Schneeweiss, Andreas and Tesch, Hans and Lichtenegger, Werner and Fehm, Tanja and Heinrich, Georg and Rezai, Mahdi and Beckmann, Matthias and Janni, Wolfgang and Weinshilboum, Richard M. and Wang, Liewei},
doi = {10.18632/oncotarget.17726},
faupublication = {yes},
journal = {Oncotarget},
note = {EVALuna2:9381},
pages = {78133-78143},
peerreviewed = {Yes},
title = {{Clinical} validation of genetic variants associated with in vitro chemotherapy-related lymphoblastoid cell toxicity},
volume = {8},
year = {2017}
}
@article{faucris.121926904,
abstract = {Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans.},
author = {Schaffer, Ashleigh E. and Eggens, Veerle R. C. and Caglayan, Ahmet Okay and Reuter, Miriam and Scott, Eric and Coufal, Nicole G. and Silhavy, Jennifer L. and Xue, Yuanchao and Kayserili, Hulya and Yasuno, Katsuhito and Rosti, Rasim Ozgur and Abdellateef, Mostafa and Caglar, Caner and Kasher, Paul R. and Cazemier, J. Leonie and Weterman, Marian A. and Cantagrel, Vincent and Cai, Na and Zweier, Christiane and Altunoglu, Umut and Satkin, N. Bilge and Aktar, Fesih and Tuysuz, Beyhan and Yalcinkaya, Cengiz and Caksen, Huseyin and Bilguvar, Kaya and Fu, Xiang-Dong and Trotta, Christopher R. and Gabriel, Stacey and Reis, André and Gunel, Murat and Baas, Frank and Gleeson, Joseph G.},
doi = {10.1016/j.cell.2014.03.049},
faupublication = {yes},
journal = {Cell},
note = {EVALuna2:9222},
pages = {651-63},
peerreviewed = {Yes},
title = {{CLP1} founder mutation links {tRNA} splicing and maturation to cerebellar development and neurodegeneration},
volume = {157},
year = {2014}
}
@article{faucris.252989574,
abstract = {We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.},
author = {Kapoor, Pooja Middha and Mavaddat, Nasim and Choudhury, Parichoy Pal and Wilcox, Amber N. and Lindström, Sara and Behrens, Sabine and Michailidou, Kyriaki and Dennis, Joe and Bolla, Manjeet K. and Wang, Qin and Jung, Audrey and Abu-Ful, Zomoroda and Ahearn, Thomas and Andrulis, Irene L. and Anton-Culver, Hoda and Arndt, Volker and Aronson, Kristan J. and Auer, Paul L. and Freeman, Laura E.Beane and Becher, Heiko and Beckmann, Matthias and Beeghly-Fadiel, Alicia and Benitez, Javier and Bernstein, Leslie and Bojesen, Stig E. and Brauch, Hiltrud and Brenner, Hermann and Brüning, Thomas and Cai, Qiuyin and Campa, Daniele and Canzian, Federico and Carracedo, Angel and Carter, Brian D. and Castelao, Jose E. and Chanock, Stephen J. and Chatterjee, Nilanjan and Chenevix-Trench, Georgia and Clarke, Christine L. and Couch, Fergus J. and Cox, Angela and Cross, Simon S. and Czene, Kamila and Dai, James Y. and Earp, H. Shelton and Ekici, Arif Bülent and Eliassen, A. Heather and Eriksson, Mikael and Evans, D. Gareth and Fasching, Peter and Figueroa, Jonine and Fritschi, Lin and Gabrielson, Marike and Gago-Dominguez, Manuela and Gao, Chi and Gapstur, Susan M. and Gaudet, Mia M. and Giles, Graham G. and González-Neira, Anna and Guénel, Pascal and Häberle, Lothar and Haiman, Christopher A. and Håkansson, Niclas and Hall, Per and Hamann, Ute and Hatse, Sigrid and Heyworth, Jane and Holleczek, Bernd and Hoover, Robert N. and Hopper, John L. and Howell, Anthony and Hunter, David J. and John, Esther M. and Jones, Michael E. and Kaaks, Rudolf and Keeman, Renske and Kitahara, Cari M. and Ko, Yon Dschun and Koutros, Stella and Kurian, Allison W. and Lambrechts, Diether and Le Marchand, Loic and Lee, Eunjung and Lejbkowicz, Flavio and Linet, Martha and Lissowska, Jolanta and Llaneza, Ana and MacInnis, Robert J. and Martinez, Maria Elena and Maurer, Tabea and McLean, Catriona and Neuhausen, Susan L. and Newman, William G. and Norman, Aaron and O'Brien, Katie M. and Olshan, Andrew F. and Olson, Janet E. and Olsson, Håkan and Orr, Nick and Perou, Charles M. and Pita, Guillermo and Polley, Eric C. and Prentice, Ross L. and Rennert, Gad and Rennert, Hedy S. and Ruddy, Kathryn J. and Sandler, Dale P. and Saunders, Christobel and Schoemaker, Minouk J. and Schöttker, Ben and Schumacher, Fredrick and Scott, Christopher and Scott, Rodney J. and Shu, Xiao Ou and Smeets, Ann and Southey, Melissa C. and Spinelli, John J. and Stone, Jennifer and Swerdlow, Anthony J. and Tamimi, Rulla M. and Taylor, Jack A. and Troester, Melissa A. and Vachon, Celine M. and van Veen, Elke M. and Wang, Xiaoliang and Weinberg, Clarice R. and Weltens, Caroline and Willett, Walter and Winham, Stacey J. and Wolk, Alicja and Yang, Xiaohong R. and Zheng, Wei and Ziogas, Argyrios and Dunning, Alison M. and Pharoah, Paul D.P. and Schmidt, Marjanka K. and Kraft, Peter and Easton, Douglas F. and Milne, Roger L. and García-Closas, Montserrat and Chang-Claude, Jenny},
doi = {10.1093/jnci/djaa056},
faupublication = {yes},
journal = {Journal of the National Cancer Institute},
note = {CRIS-Team Scopus Importer:2021-03-26},
pages = {329-337},
peerreviewed = {Yes},
title = {{Combined} {Associations} of a {Polygenic} {Risk} {Score} and {Classical} {Risk} {Factors} {With} {Breast} {Cancer} {Risk}},
volume = {113},
year = {2021}
}
@article{faucris.106521624,
abstract = {Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.},
author = {Van Koolwijk, Leonieke M. E. and Ramdas, Wishal D. and Ikram, M. Kamran and Jansonius, Nomdo M. and Pasutto, Francesca and Hysi, Pirro G. and Macgregor, Stuart and Janssen, Sarah F. and Hewitt, Alex W. and Viswanathan, Ananth C. and Ten Brink, Jacoline B. and Hosseini, S. Mohsen and Amin, Najaf and Despriet, Dominiek D. G. and Willemse-Assink, Jacqueline J. M. and Kramer, Rogier and Rivadeneira, Fernando and Struchalin, Maksim and Aulchenko, Yurii S. and Weisschuh, Nicole and Zenkel, Matthias and Mardin, Christian Y. and Gramer, Eugen and Welge-Lüssen, Ulrich-Christoph and Montgomery, Grant W. and Carbonaro, Francis and Young, Terri L. and Bellenguez, Celine and Mcguffin, Peter and Foster, Paul J. and Topouzis, Fotis and Mitchell, Paul and Wang, Jie Jin and Wong, Tien Y. and Czudowska, Monika A. and Hofman, Albert and Uitterlinden, Andre G. and Wolfs, Roger C. W. and De Jong, Paulus T. V. M. and Oostra, Ben A. and Paterson, Andrew D. and Mackey, David A. and Bergen, Arthur A. B. and Reis, André and Hammond, Christopher J. and Vingerling, Johannes R. and Lemij, Hans G. and Klaver, Caroline C. W. and Van Duijn, Cornelia M.},
doi = {10.1371/journal.pgen.1002611},
faupublication = {yes},
journal = {PLoS Genetics},
note = {EVALuna2:9127},
pages = {e1002611},
peerreviewed = {Yes},
title = {{Common} genetic determinants of intraocular pressure and primary open-angle glaucoma},
volume = {8},
year = {2012}
}
@article{faucris.106521184,
abstract = {Open-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma. The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR. We performed a meta-analysis using data from six independent studies including: the Rotterdam Study (n= 5736), Genetic Research in Isolated Populations combined with Erasmus Rucphen Family study (n= 1750), Amsterdam Glaucoma Study (n= 296) and cohorts from Erlangen and Tübingen (n= 1363), Southampton (n= 702) and deCODE (n= 36 151) resulting in a total of 3161 glaucoma cases and 42 837 controls. Of the eight loci, we found significant evidence (P= 1.41 × 10(-8)) for the association of CDKN2B with glaucoma [odds ratio (OR) for those homozygous for the risk allele: 0.76; 95% confidence interval (CI): 0.70-0.84], for the role of ATOH7 (OR: 1.28; 95% CI: 1.12-1.47) and for SIX1 (OR: 1.20; 95% CI: 1.10-1.31) when adjusting for the number of tested loci. Furthermore, there was a borderline significant association of CDC7/TGFBR3 and SALL1 (both P= 0.04) with glaucoma. In conclusion, we found consistent evidence for three common variants (CDKN2B, ATOH7 and SIX1) significantly associated with glaucoma. These findings may shed new light on the pathophysiological protein pathways leading to glaucoma, and point to pathways involved in the growth and development of the optic nerve.},
author = {Ramdas, Wishal D. and Van Koolwijk, Leonieke M. E. and Lemij, Hans G. and Pasutto, Francesca and Cree, Angela J. and Thorleifsson, Gudmar and Janssen, Sarah F. and Jacoline, Ten Brink and Amin, Najaf and Rivadeneira, Fernando and Wolfs, Roger C. W. and Walters, G. Bragi and Jonasson, Fridbert and Weisschuh, Nicole and Mardin, Christian Y. and Gibson, Jane and Zegers, Richard H. C. and Hofman, Albert and De Jong, Paulus T. V. M. and Uitterlinden, Andre G. and Oostra, Ben A. and Thorsteinsdottir, Unnur and Gramer, Eugen and Welge-Lüssen, Ulrich-Christoph and Kirwan, James F. and Bergen, Arthur A. B. and Reis, André and Stefansson, Kari and Lotery, Andrew J. and Vingerling, Johannes R. and Jansonius, Nomdo M. and Klaver, Caroline C. W. and Van Duijn, Cornelia M.},
doi = {10.1093/hmg/ddr120},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:9086},
pages = {2464-2471},
peerreviewed = {Yes},
title = {{Common} genetic variants associated with open-angle glaucoma},
volume = {20},
year = {2011}
}
@article{faucris.122346884,
abstract = {Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.},
author = {Chornokur, Ganna and Lin, Hui-Yi and Tyrer, Jonathan P. and Lawrenson, Kate and Dennis, Joe and Amankwah, Ernest K. and Qu, Xiaotao and Tsai, Ya-Yu and Jim, Heather S. L. and Chen, Zhihua and Chen, Ann Y. and Permuth-Wey, Jennifer and Aben, Katja K. H. and Anton-Culver, Hoda and Antonenkova, Natalia and Bruinsma, Fiona and Bandera, Elisa V. and Bean, Yukie T. and Beckmann, Matthias and Bisogna, Maria and Bjorge, Line and Bogdanova, Natalia and Brinton, Louise A. and Brooks-Wilson, Angela and Bunker, Clareann H. and Butzow, Ralf and Campbell, Ian G. and Carty, Karen and Chang-Claude, Jenny and Cook, Linda S. and Cramer, Daniel W. and Cunningham, Julie M. and Cybulski, Cezary and Dansonka-Mieszkowska, Agnieszka and Du Bois, Andreas and Despierre, Evelyn and Dicks, Ed and Doherty, Jennifer A. and Dork, Thilo and Durst, Matthias and Easton, Douglas F. and Eccles, Diana M. and Edwards, Robert P. and Ekici, Arif Bülent and Fasching, Peter and Fridley, Brooke L. and Gao, Yu-Tang and Gentry-Maharaj, Aleksandra and Giles, Graham G. and Glasspool, Rosalind and Goodman, Marc T. and Gronwald, Jacek and Harrington, Patricia and Harter, Philipp and Hein, Alexander and Heitz, Florian and Hildebrandt, Michelle A. T. and Hillemanns, Peter and Hogdall, Claus K. and Hogdall, Estrid and Hosono, Satoyo and Jakubowska, Anna and Jensen, Allan and Ji, Bu-Tian and Karlan, Beth Y. and Kelemen, Linda E. and Kellar, Mellissa and Kiemeney, Lambertus A. and Krakstad, Camilla and Kjaer, Susanne K. and Kupryjanczyk, Jolanta and Lambrechts, Diether and Lambrechts, Sandrina and Le, Nhu D. and Lee, Alice W. and Lele, Shashi and Leminen, Arto and Lester, Jenny and Levine, Douglas A. and Liang, Dong and Lim, Boon Kiong and Lissowska, Jolanta and Lu, Karen and Lubinski, Jan and Lundvall, Lene and Massuger, Leon F. A. G. and Matsuo, Keitaro and Mcguire, Valerie and Mclaughlin, John R. and Mcneish, Iain and Menon, Usha and Milne, Roger L. and Modugno, Francesmary and Moysich, Kirsten B. and Ness, Roberta B. and Nevanlinna, Heli and Eilber, Ursula and Odunsi, Kunle and Olson, Sara H. and Orlow, Irene and Orsulic, Sandra and Weber, Rachel Palmieri and Paul, James and Pearce, Celeste L. and Pejovic, Tanja and Pelttari, Liisa M. and Pike, Malcolm C. and Poole, Elizabeth M. and Risch, Harvey A. and Rosen, Barry and Rossing, Mary Anne and Rothstein, Joseph H. and Rudolph, Anja and Runnebaum, Ingo B. and Rzepecka, Iwona K. and Salvesen, Helga B. and Schernhammer, Eva and Schwaab, Ira and Shu, Xiao-Ou and Shvetsov, Yurii B. and Siddiqui, Nadeem and Sieh, Weiva and Song, Honglin and Southey, Melissa C. and Spiewankiewicz, Beata and Sucheston, Lara and Teo, Soo-Hwang and Terry, Kathryn L. and Thompson, Pamela J. and Thomsen, Lotte and Tangen, Ingvild L. and Tworoger, Shelley S. and Van Altena, Anne M. and Vierkant, Robert A. and Vergote, Ignace and Walsh, Christine S. and Wang-Gohrke, Shan and Wentzensen, Nicolas and Whittemore, Alice S. and Wicklund, Kristine G. and Wilkens, Lynne R. and Wu, Anna H. and Wu, Xifeng and Woo, Yin-Ling and Yang, Hannah and Zheng, Wei and Ziogas, Argyrios and Hasmad, Hanis N. and Berchuck, Andrew and Iversen, Edwin S. and Schildkraut, Joellen M. and Ramus, Susan J. and Goode, Ellen L. and Monteiro, Alvaro N. A. and Gayther, Simon A. and Narod, Steven A. and Pharoah, Pauld. P. and Sellers, Thomas A. and Phelan, Catherine M.},
doi = {10.1371/journal.pone.0128106},
faupublication = {yes},
journal = {PLoS ONE},
note = {EVALuna2:9283},
pages = {e0128106},
peerreviewed = {Yes},
title = {{Common} {Genetic} {Variation} {In} {Cellular} {Transport} {Genes} and {Epithelial} {Ovarian} {Cancer} ({EOC}) {Risk}},
volume = {10},
year = {2015}
}
@article{faucris.108984524,
abstract = {Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium.A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect.Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease.Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.},
author = {Pirie, Ailith and Guo, Qi and Kraft, Peter and Canisius, Sander and Eccles, Diana M. and Rahman, Nazneen and Nevanlinna, Heli and Chen, Constance and Khan, Sofia and Tyrer, Jonathan and Bolla, Manjeet K. and Wang, Qin and Dennis, Joe and Michailidou, Kyriaki and Lush, Michael and Dunning, Alison M. and Shah, Mitul and Czene, Kamila and Darabi, Hatef and Eriksson, Mikael and Lambrechts, Dieter and Weltens, Caroline and Leunen, Karin and Van Ongeval, Chantal and Nordestgaard, Borge G. and Nielsen, Sune F. and Flyger, Henrik and Rudolph, Anja and Seibold, Petra and Flesch-Janys, Dieter and Blomqvist, Carl and Aittomaki, Kristiina and Fagerholm, Rainer and Muranen, Taru A. and Olsen, Janet E. and Hallberg, Emily and Vachon, Celine and Knight, Julia A. and Glendon, Gord and Mulligan, Anna Marie and Broeks, Annegien and Cornelissen, Sten and Haiman, Christopher A. and Henderson, Brian E. and Schumacher, Frederick and Le Marchand, Loic and Hopper, John L. and Tsimiklis, Helen and Apicella, Carmel and Southey, Melissa C. and Cross, Simon S. and Reed, Malcolm W. R. and Giles, Graham G. and Milne, Roger L. and Mclean, Catriona and Winqvist, Robert and Pylkas, Katri and Jukkola-Vuorinen, Arja and Grip, Mervi and Hooning, Maartje J. and Hollestelle, Antoinette and Martens, John W. M. and Van Den Ouweland, Ans M. W. and Marme, Federick and Schneeweiss, Andreas and Yang, Rongxi and Burwinkel, Barbara and Figueroa, Jonine and Chanock, Stephen J. and Lissowska, Jolanta and Sawyer, Elinor J. and Tomlinson, Ian and Kerin, Michael J. and Miller, Nicola and Brenner, Hermann and Butterbach, Katja and Holleczek, Bernd and Kataja, Vesa and Kosma, Veli-Matti and Hartikainen, Jaana M. and Li, Jingmei and Brand, Judith S. and Humphreys, Keith and Devilee, Peter and Tollenaar, Robert A. E. M. and Seynaeve, Caroline and Radice, Paolo and Peterlongo, Paolo and Manoukian, Siranoush and Ficarazzi, Filomena and Beckmann, Matthias and Hein, Alexander and Ekici, Arif Bülent and Balleine, Rosemary and Phillips, Kelly-Anne and Benitez, Javier and Zamora, M. Pilar and Perez, Jose Ignacio Arias and Menendez, Primitiva and Jakubowska, Anna and Lubinski, Jan and Gronwald, Jacek and Durda, Katarzyna and Hamann, Ute and Kabisch, Maria and Ulmer, Hans Ulrich and Ruediger, Thomas and Margolin, Sara and Kristensen, Vessela and Nord, Siljie and Evans, D. Gareth and Abraham, Jean and Earl, Helena and Poole, Christopher J. and Hiller, Louise and Dunn, Janet A. and Bowden, Sarah and Yang, Rose and Campa, Daniele and Diver, W. Ryan and Gapstur, Susan M. and Gaudet, Mia M. and Hankinson, Susan and Hoover, Robert N. and Husing, Anika and Kaaks, Rudolf and Machiela, Mitchell J. and Willett, Walter and Barrdahl, Myrto and Canzian, Federico and Chin, Suet-Feung and Caldas, Carlos and Hunter, David J. and Lindstrom, Sara and Garcia-Closas, Montserrat and Couch, Fergus J. and Chenevix-Trench, Georgia and Mannermaa, Arto and Andrulis, Irene L. and Hall, Per and Chang-Claude, Jenny and Easton, Douglas F. and Bojesen, Stig E. and Cox, Angela and Fasching, Peter and Pharoah, Paul D. P. and Schmidt, Marjanka K.},
doi = {10.1186/s13058-015-0570-7},
faupublication = {yes},
journal = {Breast Cancer Research},
note = {EVALuna2:9296},
pages = {58},
peerreviewed = {Yes},
title = {{Common} germline polymorphisms associated with breast cancer-specific survival},
volume = {17},
year = {2015}
}
@inproceedings{faucris.248109427,
address = {LONDON},
author = {Hüffmeier, Ulrike and Löhr, Sabine and Uebe, Steffen and Popp, Bernt and Bowes, J. and Kirchner, P. and Giardina, E. and Korendowych, E. and Ekici, Arif Bülent and Ho, P. and Behrens, F. and Koehm, M. and Schett, Georg and Rech, Jürgen and Assmann, G. and Nimeh, A. and Padyukov, L. and Alenius, G. and Mchugh, N. J. and Sticht, Heinrich and Burkhardt, H. and Barton, A. and Reis, André},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {314-315},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Common} {RUNX3} missense variant contributes to psoriatic arthritis by affecting splicing and modifying signaling, activation and differentiation of {T}-cells},
year = {2020}
}
@inproceedings{faucris.274483199,
address = {LONDON},
author = {Kerker, Iris and Löhr, Sabine and Uebe, Steffen and Popp, Bernt and Vasileiou, Georgia and Bowes, John and Kirchner, Philipp and Becker, Ina and Giardina, Emiliano and Korendowych, Eleanor and Ekici, Arif Bülent and Ho, Pauline and Behrens, Frank and Kohm, Michaela and Schett, Georg and Rech, Jürgen and Assmann, Gunter and Nimeh, Ali and Padyukov, Leonid and Alenius, Gerd-Marie and Mchugh, Neil J. and Sticht, Heinrich and Frey, Benjamin and Burkhardt, Harald and Barton, Anne and Wiesmann da Silva Reis, André and Hüffmeier, Ulrike},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2022-05-06},
pages = {554-555},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Common} {RUNX3} missense variant contributes to psoriatic arthritis by modifying differentiation of {CD8}(+) {T}-cells},
year = {2022}
}
@article{faucris.263735026,
abstract = {Research question: Which is the optimal extraction method for isolating and quantifying circulating cell-free DNA (ccfDNA) from patients with endometriosis? Endometriosis is a common benign disease, associated with pain, infertility and reduced quality of life. Endometriosis is also a known risk factor for various cancers. Robust biomarkers for early detection and prediction of prognosis, however, are lacking. CcfDNA is an easy to obtain biomarker associated with prognosis of cancer patients and enables non-invasive analysis of somatic mutations. Recently, elevated levels of ccfDNA were detected in patients with endometriosis. Design: Two different ccfDNA extraction methods were compared: Maxwell RSC ccfDNA plasma kit (Maxwell) and QiAamp minElute ccfDNA mini kit (QIAamp). The ccfDNA and circulating mitochondrial DNA (mtDNA) quantities from 34 patients diagnosed with endometriosis were analysed. Fluorometric measurement and quantitative reverse transcription polymerase chain reaction (qRT-PCR) of short and long ALU and mtDNA fragments were used to quantiy ccfDNA. Results: The yield of ccfDNA isolated with the Maxwell method was significantly higher compared with the QIAamp method (P < 0.0001). Integrity of ccfDNA was significantly higher in the QIAamp isolate (P < 0.0001). Recovered mtDNA was not significantly different between both extraction methods used. Conclusions: The choice of extraction method can significantly influence the ccfDNA output and integrity. Both methods, however, enabled isolation of sufficient ccfDNA for further downstream applications. With this approach, isolation of ccfDNA could enable the non-invasive detection and analysis of somatic mutation within endometriosis tissue.},
author = {Hübner, Hanna and Lubrich, Hannah and Blum, Simon and Antoniadis, Sophia and Lermann, Johannes and Ekici, Arif Bülent and Fasching, Peter and Beckmann, Matthias and Rübner, Matthias and Burghaus, Stefanie},
doi = {10.1016/j.rbmo.2021.08.004},
faupublication = {yes},
journal = {Reproductive Biomedicine Online},
keywords = {CcfDNA; Circulating cell-free DNA; Endometriosis; Mitochondrial DNA; Plasma; Quantification},
note = {CRIS-Team Scopus Importer:2021-09-10},
peerreviewed = {Yes},
title = {{Comparison} of methods for isolation and quantification of circulating cell-free {DNA} from patients with endometriosis},
year = {2021}
}
@article{faucris.123483844,
abstract = {Germline mutation testing in patients with colorectal cancer (CRC) is offered only to a subset of patients with a clinical presentation or tumor histology suggestive of familial CRC syndromes, probably underestimating familial CRC predisposition. The aim of our study was to determine whether unbiased screening of newly diagnosed CRC cases with next generation sequencing (NGS) increases the overall detection rate of germline mutations. We analyzed 152 consecutive CRC patients for germline mutations in 18 CRC-associated genes using NGS. All patients were also evaluated for Bethesda criteria and all tumors were investigated for microsatellite instability, immunohistochemistry for mismatch repair proteins and the BRAF*V600E somatic mutation. NGS based sequencing identified 27 variants in 9 genes in 23 out of 152 patients studied (18%). Three of them were already reported as pathogenic and 12 were class 3 germline variants with an uncertain prediction of pathogenicity. Only 1 of these patients fulfilled Bethesda criteria and had a microsatellite instable tumor and an MLH1 germline mutation. The others would have been missed with current approaches: 2 with a MSH6 premature termination mutation and 12 uncertain, potentially pathogenic class 3 variants in APC, MLH1, MSH2, MSH6, MSH3 and MLH3. The higher NGS mutation detection rate compared with current testing strategies based on clinicopathological criteria is probably due to the large genetic heterogeneity and overlapping clinical presentation of the various CRC syndromes. It can also identify apparently nonpenetrant germline mutations complicating the clinical management of the patients and their families.},
author = {Kraus, Cornelia and Rau, Tilman and Lux, Philipp and Erlenbach-Wuensch, Katharina and Loehr, Sabine and Krumbiegel, Mandy and Thiel, Christian and Stoehr, Robert and Agaimy, Abbas and Croner, Roland S. and Stürzl, Michael and Hohenberger, Werner and Hartmann, Arndt and Reis, André},
doi = {10.1002/ijc.29149},
faupublication = {yes},
journal = {International Journal of Cancer},
note = {EVALuna2:6598},
pages = {E559-68},
peerreviewed = {Yes},
title = {{Comprehensive} screening for mutations associated with colorectal cancer in unselected cases reveals penetrant and nonpenetrant mutations},
volume = {136},
year = {2015}
}
@article{faucris.316777005,
abstract = {Numerous contiguous gene deletion syndromes causing neurodevelopmental disorders have previously been defined using cytogenetics for which only in the current genomic era the disease-causing genes have become elucidated. One such example is deletion at Xq22.2, previously associated with a neurodevelopmental disorder which has more recently been found to be caused by de novo loss-of-function variants in TCEAL1. So far, a single study reported six unrelated individuals with this monogenetic disorder, presenting with syndromic features including developmental delay especially affecting expressive speech, intellectual disability, autistic-like behaviors, hypotonia, gait abnormalities and mild facial dysmorphism, in addition to ocular, gastrointestinal, and immunologic abnormalities. Here we report on four previously undescribed individuals, including two adults, with de novo truncating variants in TCEAL1, identified through trio exome or genome sequencing, further delineating the phenotype of the TCEAL1-related disorder. Whereas overall we identify similar features compared to the original report, we also highlight features in our adult individuals including hyperphagia, obesity, and endocrine abnormalities including hyperinsulinemia, hyperandrogenemia, and polycystic ovarian syndrome. X chromosome inactivation and RNA-seq studies further provide functional insights in the molecular mechanisms. Together this report expands the phenotypic and molecular spectrum of the TCEAL1-related disorder which will be useful for counseling of newly identified individuals and their families.},
author = {Albuainain, Fatimah and Shi, Yuwei and Lor-Zade, Sarah and Hüffmeier, Ulrike and Pauly, Melissa and Reis, André and Faivre, Laurence and Maraval, Julien and Bruel, Ange Line and Them, Frédéric Tran Mau and Haack, Tobias B. and Grasshoff, Ute and Horber, Veronka and Schot, Rachel and van Slegtenhorst, Marjon and Wilke, Martina and Barakat, Tahsin Stefan},
doi = {10.1038/s41431-023-01530-6},
faupublication = {yes},
journal = {European Journal of Human Genetics},
note = {CRIS-Team Scopus Importer:2024-01-19},
peerreviewed = {Yes},
title = {{Confirmation} and expansion of the phenotype of the {TCEAL1}-related neurodevelopmental disorder},
year = {2024}
}
@article{faucris.265522797,
abstract = {In the published original paper, Fig. 1 is incomplete. Only Fig. 1a is shown. This erratum corrects Fig. 1 and adds the missing panel 1 b-f to the article.},
author = {Averdunk, Luisa and Sticht, Heinrich and Surowy, Harald and Luedecke, Hermann-Josef and Koch-Hogrebe, Margarete and Alsaif, Hessa S. and Kahrizi, Kimia and Alzaidan, Hamad and Alawam, Bashayer S. and Tohary, Mohamed and Kraus, Cornelia and Endele, Sabine and Wadman, Erin and Kaplan, Julie D. and Efthymiou, Stephanie and Najmabadi, Hossein and Reis, André and Alkuraya, Fowzan S. and Wieczorek, Dagmar},
doi = {10.1007/s00109-021-02153-4},
faupublication = {yes},
journal = {Journal of Molecular Medicine},
note = {CRIS-Team Scopus Importer:2021-10-29},
peerreviewed = {Yes},
title = {{Correction} to: {The} recurrent missense mutation p.({Arg367Trp}) in {YARS1} causes a distinct neurodevelopmental phenotype ({Journal} of {Molecular} {Medicine}, (2021), 10.1007/s00109-021-02124-9)},
year = {2021}
}
@article{faucris.254726322,
abstract = {An amendment to this paper has been published and can be accessed via the original article.},
author = {Gombert, Sara and Rhein, Mathias and Winterpacht, Andreas and Münster, Tino and Hillemacher, Thomas and Leffler, Andreas and Frieling, Helge},
doi = {10.1186/s13148-021-01059-9},
faupublication = {yes},
journal = {Clinical Epigenetics},
note = {CRIS-Team Scopus Importer:2021-04-09},
peerreviewed = {Yes},
title = {{Correction} to: {Transient} receptor potential ankyrin 1 promoter methylation and peripheral pain sensitivity in {Crohn}’s disease ({Clinical} {Epigenetics}, (2020), 12, 1, (1), 10.1186/s13148-019-0796-9)},
volume = {13},
year = {2021}
}
@article{faucris.226997490,
abstract = {BACKGROUND: Growing demand for risk-reducing surgery in individuals with inherited susceptibility to cancer leads to the question whether these procedures are cost effective for the executing hospitals. This study compared the clinical costs for bilateral risk-reducing mastectomy (BRRM) with and without different types of reconstruction, risk-reducing salpingo-oophorectomy (RRSO), and their combinations with corresponding reimbursements in the statutory health-care system in Germany. PATIENTS AND METHODS: Real total costs of care for BRRM with and without reconstruction, RRSO, and their combinations were calculated as the sum of all personnel and technical costs. These costs calculated in a German University hospital were compared with the sum of all reimbursements in the German DRG-based health-care system. RESULTS: While sole RRSO, BRRM without reconstruction, and BRRM with secondary DIEP (deep inferior epigastric perforator)-reconstruction still result in a small benefit, we even found shortfalls for the hospital with all other prophylactic operations under consideration. The calculated deficits were especially high for BRRM with implant-based breast reconstruction and for combined operations when the risk reduction is achieved with a minimum of separate operations. CONCLUSIONS: Risk-reducing surgery in BRCA-mutation carriers is frequently not cost-covering for the executing hospitals in the German health-care system. Thus, appropriate concepts are required to ensure a nationwide care.},
author = {Schrauder, Michael G. and Brunel-Geuder, Lisa and Häberle, Lothar and Wunderle, Marius and Hoyer, Juliane and Csorba, Roland and Reis, André and Schulz-Wendtland, Rüdiger and Beckmann, Matthias and Lux, Michael P.},
doi = {10.1186/s40001-019-0391-8},
faupublication = {yes},
journal = {European Journal of Medical Research},
keywords = {BRCA; Breast cancer; Cost effectiveness; Genetic counseling; Ovarian cancer},
note = {CRIS-Team Scopus Importer:2019-09-24},
pages = {32-},
peerreviewed = {unknown},
title = {{Cost} effectiveness of bilateral risk-reducing mastectomy and salpingo-oophorectomy},
volume = {24},
year = {2019}
}
@article{faucris.122612424,
abstract = {Risk-reducing surgeries are a feasible option for mitigating the risk in individuals with inherited susceptibility to cancer, but are the procedures cost-effective in the current health-care system in Germany? This study compared the health-care costs for bilateral risk-reducing mastectomy (BRRM) and risk-reducing (bilateral) salpingo-oophorectomy (RRSO) with cancer treatment costs that could potentially be prevented.The analysis is based on interdisciplinary consultations with individuals with a high familial risk for breast and ovarian cancer at the University Breast Center for Franconia (Germany) between 2009 and 2013 (370 consultations; 44 patients with BRCA1 mutations and 26 with BRCA2 mutations). Health-care costs for risk-reducing surgeries in BRCA mutation carriers were calculated as reimbursements in the German diagnosis-related groups (DRG) hospital pricing system. These costs for the health-care system were compared with the potential cancer treatment costs that could possibly be prevented by risk-reducing surgeries.Long-term health-care costs can be reduced by risk-reducing surgeries after genetic testing in BRCA mutation carriers. The health-care system in Germany would have saved EUR 136,295 if BRRM had been performed and EUR 791,653 if RRSO had been performed before the development of cancer in only 50% of the 70 mutation carriers seen in our center. Moreover, in patients with combined RRSO and BRRM (without breast reconstruction), one further life-year for a 40-year-old BRCA mutation carrier would cost EUR 2,183.Intensive care, including risk-reducing surgeries in BRCA mutation carriers, is cost-effective from the point of view of the health-care system in Germany.},
author = {Schrauder, Michael G. and Brunel-Geuder, Lisa and Häberle, Lothar and Wunderle, Marius and Hoyer, Juliane and Wiesmann da Silva Reis, André and Schulz-Wendtland, Rüdiger and Beckmann, Matthias and Lux, Michael P.},
doi = {10.1016/j.breast.2017.02.008},
faupublication = {yes},
journal = {BREAST },
note = {EVALuna2:9369},
pages = {186-191},
peerreviewed = {Yes},
title = {{Cost}-effectiveness of risk-reducing surgeries in preventing hereditary breast and ovarian cancer},
volume = {32},
year = {2017}
}
@article{faucris.287837650,
abstract = {C-terminal Binding Protein 1 (CTBP1) is a ubiquitously expressed transcriptional co-repressor and membrane trafficking regulator. A recurrent de novo c.991C>T mutation in CTBP1 leads to expression of p.R331W CTBP1 and causes hypotonia, ataxia, developmental delay, and tooth enamel defects syndrome (HADDTS), a rare early onset neurodevelopmental disorder. We generated hESCs lines with heterozygote and homozygote c.991C>T in CTBP1 using CRISPR/Cas9 genome editing and validated them for genetic integrity, off-target mutations, and pluripotency. They will be useful for investigation of HADDTS pathophysiology and for screening for potential therapeutics.},
author = {Akdas, Enes Yagiz and Turan, Sören and Guhathakurta, Debarpan and Ekici, Arif Bülent and Salar, Seda and Lie, Dieter Chichung and Winner, Beate and Fejtová, Anna},
doi = {10.1016/j.scr.2022.103012},
faupublication = {yes},
journal = {Stem Cell Research},
note = {CRIS-Team Scopus Importer:2023-01-20},
pages = {103012},
peerreviewed = {Yes},
title = {{CRISPR}/{Cas9}-mediated generation of {hESC} lines with homozygote and heterozygote p.{R331W} mutation in {CTBP1} to model {HADDTS} syndrome},
volume = {67},
year = {2023}
}
@article{faucris.303972051,
abstract = {C-terminal Binding Protein 1 (CTBP1) is a ubiquitously expressed transcriptional co-repressor and membrane trafficking regulator. A recurrent de novo c.991C>T mutation in CTBP1 leads to expression of p.R331W CTBP1 and causes hypotonia, ataxia, developmental delay, and tooth enamel defects syndrome (HADDTS), a rare early onset neurodevelopmental disorder. We generated hESCs lines with heterozygote and homozygote c.991C>T in CTBP1 using CRISPR/Cas9 genome editing and validated them for genetic integrity, off-target mutations, and pluripotency. They will be useful for investigation of HADDTS pathophysiology and for screening for potential therapeutics.},
author = {Winner, Beate and Akdas, Enes Yagiz and Turan, Sören and Guhathakurta, Debarpan and Ekici, Arif Bülent and Salar, Seda and Lie, Dieter Chichung and Fejtová, Anna},
doi = {10.1016/j.scr.2022.103012},
faupublication = {yes},
journal = {Stem Cell Research},
pages = {103012},
peerreviewed = {Yes},
title = {{CRISPR}/{Cas9}-mediated generation of {hESC} lines with homozygote and heterozygote p.{R331W} mutation in {CTBP1} to model {HADDTS} syndrome.},
url = {https://www.sciencedirect.com/science/article/pii/S1873506122003610?via=ihub},
volume = {67},
year = {2023}
}
@article{faucris.252771775,
abstract = {ARID1B haploinsufficiency induced by missense or nonsense mutations of ARID1B is a cause of Coffin-Siris syndrome (CSS), a neurodevelopmental disorder associated with intellectual disability. At present, no appropriate human stem cell model for ARID1B-associated CSS has been reported. Here, we describe the generation and validation of ARID1B(+/-) hESCs by introducing out of frame deletions into exon 5 or 6 of ARID1B with CRISPR/Cas9 genome editing. These ARID1B(+/-) hESC lines allow to study the pathophysiology of ARID1B-associated CSS in 2D and 3D models of human neurodevelopment.},
author = {Börstler, Tom and Wend, Holger and Krumbiegel, Mandy and Kavyanifar, Atria and Wiesmann da Silva Reis, André and Lie, Dieter Chichung and Winner, Beate and Turan, Sören},
doi = {10.1016/j.scr.2020.101889},
faupublication = {yes},
journal = {Stem Cell Research},
peerreviewed = {Yes},
title = {{CRISPR}/{Cas9} mediated generation of human {ARID1B} heterozygous knockout {hESC} lines to model {Coffin}-{Siris} syndrome},
volume = {47},
year = {2020}
}
@article{faucris.240762268,
abstract = {ARID1B haploinsufficiency induced by missense or nonsense mutations of ARID1B is a cause of Coffin-Siris syndrome (CSS), a neurodevelopmental disorder associated with intellectual disability. At present, no appropriate human stem cell model for ARID1B-associated CSS has been reported. Here, we describe the generation and validation of ARID1B+/- hESCs by introducing out of frame deletions into exon 5 or 6 of ARID1B with CRISPR/Cas9 genome editing. These ARID1B+/- hESC lines allow to study the pathophysiology of ARID1B-associated CSS in 2D and 3D models of human neurodevelopment.},
author = {Börstler, Tom and Wend, Holger and Krumbiegel, Mandy and Kavyanifar, Atria and Reis, André and Lie, Dieter Chichung and Winner, Beate and Turan, Sören},
doi = {10.1016/j.scr.2020.101889},
faupublication = {yes},
journal = {Stem Cell Research},
note = {CRIS-Team Scopus Importer:2020-07-24},
peerreviewed = {Yes},
title = {{CRISPR}/{Cas9} mediated generation of human {ARID1B} heterozygous knockout {hESC} lines to model {Coffin}-{Siris} syndrome},
volume = {47},
year = {2020}
}
@article{faucris.293206399,
abstract = {ARID1B haploinsufficiency induced by missense or nonsense mutations of
ARID1B is a cause of Coffin-Siris syndrome (CSS), a neurodevelopmental
disorder associated with intellectual disability. At present, no
appropriate human stem cell model for ARID1B-associated CSS has been
reported. Here, we describe the generation and validation of ARID1B+/- hESCs by introducing out of frame deletions into exon 5 or 6 of ARID1B with CRISPR/Cas9 genome editing. These ARID1B+/- hESC lines allow to study the pathophysiology of ARID1B-associated CSS in 2D and 3D models of human neurodevelopment.},
author = {Turan, Soeren and Winner, Beate and Winner, Beate and Krumbiegel, Mandy and Wiesmann da Silva Reis, André and Lie, Dieter Chichung and Börstler, Tom and Wend, Holger and Krumbiegel, Mandy and Kavyanifar, Atria and Reis, Andre and Lie, Dieter Chichung},
doi = {10.1016/j.scr.2020.101889},
faupublication = {yes},
journal = {Stem Cell Research},
pages = {101889},
peerreviewed = {Yes},
title = {{CRISPR}/{Cas9} mediated generation of human {ARID1B} heterozygous knockout {hESC} lines to model {Coffin}-{Siris} syndrome.},
volume = {47},
year = {2020}
}
@article{faucris.249338209,
abstract = {The HIV-1 Rev protein is a nuclear export factor for unspliced and incom-pletely spliced HIV-1 RNAs. Without Rev, these intron-retaining RNAs are trapped in the nucleus. A genome-wide screen identified nine proteins of the spliceosome, which all enhanced expression from the HIV-1 unspliced RNA after CRISPR/Cas knockdown. Depletion of DHX38, WDR70, and four proteins of the Prp19-associated complex (ISY1, BUD31, XAB2, and CRNKL1) resulted in a more than 20-fold enhancement of unspliced HIV-1 RNA levels in the cytoplasm. Targeting of CRNKL1, DHX38, and BUD31 affected nuclear export efficiencies of the HIV-1 unspliced RNA to a much larger extent than splicing. Transcriptomic analyses further revealed that CRNKL1 also suppresses cyto-plasmic levels of a subset of cellular mRNAs, including some with selectively retained introns. Thus, CRNKL1-dependent nuclear retention is a novel cellular mechanism for the regulation of cytoplasmic levels of intron-retaining HIV-1 mRNAs, which HIV-1 may have harnessed to direct its complex splicing pattern. IMPORTANCE To regulate its complex splicing pattern, HIV-1 uses the adaptor protein Rev to shuttle unspliced or partially spliced mRNA from the nucleus to the cyto-plasm. In the absence of Rev, these RNAs are retained in the nucleus, but it is unclear why. Here we identify cellular proteins whose depletion enhances cytoplas-mic levels of the HIV-1 unspliced RNA. Depletion of one of them, CRNKL1, also increases cytoplasmic levels of a subset of intron-retaining cellular mRNA, suggesting that CRNKL1-dependent nuclear retention may be a basic cellular mechanism exploited by HIV-1.},
author = {Xiao, Han and Wyler, Emanuel and Milek, Miha and Grewe, Bastian and Kirchner, Philipp and Ekici, Arif Bülent and Silva, Ana Beatriz Oliveira Villela and Jungnickl, Doris and Full, Florian and Thomas, Marco and Landthaler, Markus and Enßer, Armin and Überla, Klaus},
doi = {10.1128/mBio.02525-20},
faupublication = {yes},
journal = {mBio},
keywords = {Association; CRNKL1; Human immunodeficiency virus; Intron-retaining RNA; Nuclear retention; RNA splicing},
month = {Jan},
note = {CRIS-Team Scopus Importer:2021-02-12},
pages = {1-24},
peerreviewed = {Yes},
title = {{Crnkl1} is a highly selective regulator of intron-retaining {HIV}-1 and cellular mrnas},
volume = {12},
year = {2021}
}
@article{faucris.221885991,
abstract = {Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function. Results: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. Conclusion: We significantly broaden the mutational and clinical spectrum of CTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.},
author = {Konrad, Enrico and Nardini, Niels and Caliebe, Almuth and Nagel, Inga and Young, Dana and Horvath, Gabriella and Santoro, Stephanie L. and Shuss, Christine and Ziegler, Alban and Bonneau, Dominique and Kempers, Marlies and Pfundt, Rolph and Legius, Eric and Bouman, Arjan and Stuurman, Kyra E. and Õunap, Katrin and Pajusalu, Sander and Wojcik, Monica H. and Vasileiou, Georgia and Le Guyader, Gwenaël and Schnelle, Hege M. and Berland, Siren and Zonneveld-Huijssoon, Evelien and Kersten, Simone and Gupta, Aditi and Blackburn, Patrick R. and Ellingson, Marissa S. and Ferber, Matthew J. and Dhamija, Radhika and Klee, Eric W. and McEntagart, Meriel and Lichtenbelt, Klaske D. and Kenney, Amy and Vergano, Samantha A. and Abou Jamra, Rami and Platzer, Konrad and Ella Pierpont, Mary and Khattar, Divya and Hopkin, Robert J. and Martin, Richard J. and Jongmans, Marjolijn C.J. and Chang, Vivian Y. and Martinez-Agosto, Julian A. and Kuismin, Outi and Kurki, Mitja I. and Pietiläinen, Olli and Palotie, Aarno and Maarup, Timothy J. and Johnson, Diana S. and Venborg Pedersen, Katja and Laulund, Lone W. and Lynch, Sally A. and Blyth, Moira and Prescott, Katrina and Canham, Natalie and Ibitoye, Rita and Brilstra, Eva H. and Shinawi, Marwan and Fassi, Emily and Sticht, Heinrich and Gregor, Anne and Van Esch, Hilde and Zweier, Christiane},
doi = {10.1038/s41436-019-0585-z},
faupublication = {yes},
journal = {Genetics in Medicine},
keywords = {chromatin organization; CTCF; Drosophila melanogaster; intellectual disability; neurodevelopmental disorders},
note = {CRIS-Team Scopus Importer:2019-07-09},
peerreviewed = {Yes},
title = {{CTCF} variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum},
year = {2019}
}
@inproceedings{faucris.265056318,
address = {ROCKVILLE},
author = {Hatami, Niloofar and Büttner, Christian and Bock, Felix and Simfors, Sara and Reis, André and Cursiefen, Claus and Clahsen, Thomas},
booktitle = {INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-10-15},
peerreviewed = {unknown},
publisher = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
title = {{Cystathionine} beta-synthase as novel regulator of lymphangiogenesis},
year = {2021}
}
@article{faucris.282408422,
abstract = {Lymphangiogenesis is a key player in several diseases such as tumor metastasis, obesity, and graft rejection. Endogenous regulation of lymphangiogenesis is only partly understood. Here we use the normally avascular cornea as a model to identify endogenous regulators of lymphangiogenesis. Quantitative trait locus analysis of a large low-lymphangiogenic BALB/cN x high-lymphangiogenic C57BL/6 N intercross and prioritization by whole-transcriptome sequencing identify a novel gene responsible for differences in lymphatic vessel architecture on chromosome 17, the cystathionine β-synthase (Cbs). Inhibition of CBS in lymphatic endothelial cells results in reduce proliferation, migration, altered tube-formation, and decrease expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGF-R2) and VEGF-R3, but not their ligands VEGF-C and VEGF-D. Also in vivo inflammation-induced lymphangiogenesis is significantly reduce in C57BL/6 N mice after pharmacological inhibition of CBS. The results confirm CBS as a novel endogenous regulator of lymphangiogenesis acting via VEGF receptor 2 and 3-regulation and open new treatment avenues in diseases associated with pathologic lymphangiogenesis.},
author = {Hatami, Niloofar and Büttner, Christian and Bock, Felix and Simfors, Sara and Musial, Gwen and Reis, André and Cursiefen, Claus and Clahsen, Thomas},
doi = {10.1038/s42003-022-03923-7},
faupublication = {yes},
journal = {Communications Biology},
note = {CRIS-Team Scopus Importer:2022-09-30},
peerreviewed = {Yes},
title = {{Cystathionine} β-synthase as novel endogenous regulator of lymphangiogenesis via modulating {VEGF} receptor 2 and 3},
volume = {5},
year = {2022}
}
@article{faucris.118700824,
abstract = {Recently, de novo heterozygous variants in DDX3X have been reported in about 1.5% of 2659 females with previously unexplained intellectual disability (ID). We report on the identification of DDX3X variants in two unrelated girls with clinical features of Toriello-Carey Syndrome (T-CS). In patient 1, the recurrent variant c.1703C>T; p.(P568L) was identified when reconsidering X-linked de novo heterozygous variants in exome sequencing data. In patient 2, the DDX3X variant c.1600C>G; p.(R534G) was also detected by exome sequencing. Based on these data, de novo heterozygous DDX3X variants should be considered not only in females with unexplained ID, but also in individuals with a clinical diagnosis of T-CS.},
author = {Dikow, Nicola and Granzow, Martin and Graul-Neumann, Luitgard M. and Karch, Stephanie and Hinderhofer, Katrin and Paramasivam, Nagarajan and Behl, Laura-Jane and Kaufmann, Lilian and Fischer, Christine and Evers, Christina and Schlesner, Matthias and Eils, Roland and Borck, Guntram and Zweier, Christiane and Bartram, Claus R. and Carey, John C. and Moog, Ute},
doi = {10.1002/ajmg.a.38164},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
note = {EVALuna2:9360},
pages = {1369-1373},
peerreviewed = {Yes},
title = {{DDX3X} mutations in two girls with a phenotype overlapping {Toriello}-{Carey} syndrome},
volume = {173},
year = {2017}
}
@article{faucris.238882440,
abstract = {Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the midbrain. In recent years, researchers have started studying PD using induced pluripotent stem cell (iPSC) models of the disease. Surprisingly, few studies have combined iPSC-technology with the so-called powerful ‘omics’ approaches. Here, we review the current state of omics applications used in combination with iPSC-derived models to study PD. Our focus is on studies investigating transcriptional changes and publications using proteomics applications. Lastly, we discuss current caveats in the field and identify potential future directions to obtain novel insights into PD pathology.},
author = {Krach, Florian and Bogiongko, Marios Evangelos and Winner, Beate},
doi = {10.1016/j.mcn.2020.103501},
faupublication = {yes},
journal = {Molecular and Cellular Neuroscience},
keywords = {Disease modeling; iPSC; Parkinson's disease; Proteomics; RNA-seq; Transcriptomics},
note = {CRIS-Team Scopus Importer:2020-06-02},
peerreviewed = {Yes},
title = {{Decoding} {Parkinson}'s disease – {iPSC}-derived models in the {OMICs} era},
volume = {106},
year = {2020}
}
@article{faucris.286389279,
abstract = {Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the midbrain. In recent years, researchers have started studying PD using induced pluripotent stem cell (iPSC) models of the disease. Surprisingly, few studies have combined iPSC-technology with the so-called powerful 'omics' approaches. Here, we review the current state of omics applications used in combination with iPSC-derived models to study PD. Our focus is on studies investigating transcriptional changes and publications using proteomics applications. Lastly, we discuss current caveats in the field and identify potential future directions to obtain novel insights into PD pathology.},
author = {Winner, Beate and Krach, Florian and Marios-Evangelos, Bogiongko},
doi = {10.1016/j.mcn.2020.103501},
faupublication = {yes},
journal = {Molecular and Cellular Neuroscience},
keywords = {Disease modeling; Parkinson's disease; Proteomics; RNA-seq; Transcriptomics; iPSC},
pages = {103501},
peerreviewed = {Yes},
title = {{Decoding} {Parkinson}'s disease - {iPSC}-derived models in the {OMICs} era.},
volume = {106},
year = {2020}
}
@article{faucris.118698404,
abstract = {Contacts between endosomes and the endoplasmic reticulum (ER) promote endosomal tubule fission, but the mechanisms involved and consequences of tubule fission failure are incompletely understood. We found that interaction between the microtubule-severing enzyme spastin and the ESCRT protein IST1 at ER-endosome contacts drives endosomal tubule fission. Failure of fission caused defective sorting of mannose 6-phosphate receptor, with consequently disrupted lysosomal enzyme trafficking and abnormal lysosomal morphology, including in mouse primary neurons and human stem cell-derived neurons. Consistent with a role for ER-mediated endosomal tubule fission in lysosome function, similar lysosomal abnormalities were seen in cellular models lacking the WASH complex component strumpellin or the ER morphogen REEP1. Mutations in spastin, strumpellin, or REEP1 cause hereditary spastic paraplegia (HSP), a disease characterized by axonal degeneration. Our results implicate failure of the ER-endosome contact process in axonopathy and suggest that coupling of ER-mediated endosomal tubule fission to lysosome function links different classes of HSP proteins, previously considered functionally distinct, into a unifying pathway for axonal degeneration.},
author = {Allison, Rachel and Edgar, James R. and Pearson, Guy and Rizo, Tania and Newton, Timothy and Guenther, Sven and Berner, Fiamma and Hague, Jennifer and Connell, James W. and Winkler, Jürgen and Lippincott-Schwartz, Jennifer and Beetz, Christian and Winner, Beate and Reid, Evan},
doi = {10.1083/jcb.201609033},
faupublication = {yes},
journal = {The Journal of Cell Biology},
note = {EVALuna2:9354},
pages = {1337-1355},
peerreviewed = {Yes},
title = {{Defects} in {ER}-endosome contacts impact lysosome function in hereditary spastic paraplegia},
volume = {216},
year = {2017}
}
@inproceedings{faucris.248094300,
address = {LONDON},
author = {Rieger, Melissa and Krumbiegel, Mandy and Reuter, Miriam and Schützenberger, Anne and Reis, André and Zweier, Christiane},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {865-866},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Deletion} 7q31.2q31.31 segregating in a family with speech and language deficiencies},
year = {2020}
}
@article{faucris.120852644,
abstract = {Marshall-Smith syndrome (MSS) is a very rare malformation syndrome characterized by typical craniofacial anomalies, abnormal osseous maturation, developmental delay, failure to thrive, and respiratory difficulties. Mutations in the nuclear factor 1/X gene (NFIX) were recently identified as the cause of MSS. In our study cohort of 17 patients with a clinical diagnosis of MSS, conventional sequencing of NFIX revealed frameshift and splice-site mutations in 10 individuals. Using multiplex ligation-dependent probe amplification analysis, we identified a recurrent deletion of NFIX exon 6 and 7 in five individuals. We demonstrate this recurrent deletion is the product of a recombination between AluY elements located in intron 5 and 7. Two other patients had smaller deletions affecting exon 6. These findings show that MSS is a genetically homogeneous Mendelian disorder. RT-PCR experiments with newly identified NFIX mutations including the recurrent exon 6 and 7 deletion confirmed previous findings indicating that MSS-associated mutant mRNAs are not cleared by nonsense-mediated mRNA decay. Predicted MSS-associated mutant NFIX proteins consistently have a preserved DNA binding and dimerization domain, whereas they grossly vary in their C-terminal portion. This is in line with the hypothesis that MSS-associated mutations encode dysfunctional proteins that act in a dominant negative manner.},
author = {Schanze, Denny and Neubauer, Dorothee and Cormier-Daire, Valerie and Delrue, Marie-Ange and Dieux-Coeslier, Anne and Hasegawa, Tomonobu and Holmberg, Eva E. and Koenig, Rainer and Krueger, Gabriele and Schanze, Ina and Seemanova, Eva and Shaw, Adam C. and Vogt, Julie and Volleth, Marianne and Reis, André and Meinecke, Peter and Hennekam, Raoul C. M. and Zenker, Martin},
doi = {10.1002/humu.22603},
faupublication = {yes},
journal = {Human Mutation},
note = {EVALuna2:9229},
pages = {1092-100},
peerreviewed = {Yes},
title = {{Deletions} in the 3' part of the {NFIX} gene including a recurrent {Alu}-mediated deletion of exon 6 and 7 account for previously unexplained cases of {Marshall}-{Smith} syndrome},
volume = {35},
year = {2014}
}
@article{faucris.315958746,
abstract = {Coffin–Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18 years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.},
author = {Schmetz, Ariane and Lüdecke, Hermann Josef and Surowy, Harald and Sivalingam, Sugirtahn and Bruel, Ange Line and Caumes, Roseline and Charles, Perrine and Chatron, Nicolas and Chrzanowska, Krystyna and Codina-Solà, Marta and Colson, Cindy and Cuscó, Ivon and Denommé-Pichon, Anne Sophie and Edery, Patrick and Faivre, Laurence and Green, Andrew and Heide, Solveig and Hsieh, Tzung Chien and Hustinx, Alexander and Kleinendorst, Lotte and Knopp, Cordula and Kraft, Florian and Krawitz, Peter M. and Lasa-Aranzasti, Amaia and Lesca, Gaetan and López-González, Vanesa and Maraval, Julien and Mignot, Cyril and Neuhann, Teresa and Netzer, Christian and Oehl-Jaschkowitz, Barbara and Petit, Florence and Philippe, Christophe and Posmyk, Renata and Putoux, Audrey and Reis, André and Sánchez-Soler, María José and Suh, Julia and Tkemaladze, Tinatin and Tran Mau Them, Frédéric and Travessa, André and Trujillano, Laura and Valenzuela, Irene and van Haelst, Mieke M. and Vasileiou, Georgia and Vincent-Delorme, Catherine and Walther, Mona and Verde, Pablo and Bramswig, Nuria C. and Wieczorek, Dagmar},
doi = {10.1007/s00439-023-02622-5},
faupublication = {yes},
journal = {Human genetics},
note = {CRIS-Team Scopus Importer:2023-12-29},
peerreviewed = {Yes},
title = {{Delineation} of the adult phenotype of {Coffin}–{Siris} syndrome in 35 individuals},
year = {2023}
}
@inproceedings{faucris.228304034,
address = {LONDON},
author = {Sa, M. J. Nabais and Venselaar, H. and Wiel, L. and Trimouille, A. and Lasseaux, E. and Naudion, S. and Lacombe, D. and Piton, A. and Vincent-Delorme, C. and Zweier, Christiane and Wiesmann da Silva Reis, André and Trollmann, Regina and Ruiz, A. and Gabau, E. and Vetro, A. and Guerrini, R. and Bakhtiari, S. and Kruer, M. and Crompton, K. and Amor, D. J. and Bijlsma, E. K. and Barakat, T. S. and Van Dooren, M. F. and Pfundt, R. and Gilissen, C. and De Vries, B. B. and De Brouwer, A. P. and Koolen, D. A.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2019-06-15/2019-06-18},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {1381-1381},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{Delineation} of the clinical phenotype caused by de novo {CLTC} variants},
venue = {Gothenburg, SWEDEN},
year = {2019}
}
@article{faucris.238710247,
abstract = {Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein inclusions mostly composed of aggregated forms of α-synuclein (α-Syn) and by the progressive degeneration of midbrain dopaminergic neurons (mDANs), resulting in motor symptoms. While other brain regions also undergo pathologic changes in PD, the relevance of α-Syn aggregation for the preferential loss of mDANs in PD pathology is not completely understood yet. To elucidate the mechanisms of the brain region-specific neuronal vulnerability in PD, we modeled human PD using human-induced pluripotent stem cells (iPSCs) from familial PD cases with a duplication (Dupl) of the α-Syn gene (SNCA) locus. Human iPSCs from PD Dupl patients and a control individual were differentiated into mDANs and cortical projection neurons (CPNs). SNCA dosage increase did not influence the differentiation efficiency of mDANs and CPNs. However, elevated α-Syn pathology, as revealed by enhanced α-Syn insolubility and phosphorylation, was determined in PD-derived mDANs compared with PD CPNs. PD-derived mDANs exhibited higher levels of reactive oxygen species and protein nitration levels compared with CPNs, which might underlie elevated α-Syn pathology observed in mDANs. Finally, increased neuronal death was observed in PD-derived mDANs compared to PD CPNs and to control mDANs and CPNs. Our results reveal, for the first time, a higher α-Syn pathology, oxidative stress level, and neuronal death rate in human PD mDANs compared with PD CPNs from the same patient. The finding implies the contribution of pathogenic α-Syn, probably induced by oxidative stress, to selective vulnerability of substantia nigra dopaminergic neurons in human PD.},
author = {Brazdis, Razvan Marius and Alecu, Julian E. and Marsch, Daniel and Dahms, Annika and Simmnacher, Katrin and Lörentz, Sandra and Brendler, Anna and Schneider, Yanni and Marxreiter, Franz and Roybon, Laurent and Winner, Beate and Xiang, Wei and Prots, Iryna},
doi = {10.1093/hmg/ddaa039},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {CRIS-Team Scopus Importer:2020-05-26},
pages = {1180-1191},
peerreviewed = {Yes},
title = {{Demonstration} of brain region-specific neuronal vulnerability in human {iPSC}-based model of familial {Parkinson}'s disease},
volume = {29},
year = {2020}
}
@article{faucris.229751916,
abstract = {Purpose: Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous neurodevelopmental disorders. We sought to delineate the clinical, molecular, and neuroimaging spectrum of a novel neurodevelopmental disorder caused by variants in the zinc finger protein 292 gene (ZNF292). Methods: We ascertained a cohort of 28 families with ID due to putatively pathogenic ZNF292 variants that were identified via targeted and exome sequencing. Available data were analyzed to characterize the canonical phenotype and examine genotype–phenotype relationships. Results: Probands presented with ID as well as a spectrum of neurodevelopmental features including ASD, among others. All ZNF292 variants were de novo, except in one family with dominant inheritance. ZNF292 encodes a highly conserved zinc finger protein that acts as a transcription factor and is highly expressed in the developing human brain supporting its critical role in neurodevelopment. Conclusion: De novo and dominantly inherited variants in ZNF292 are associated with a range of neurodevelopmental features including ID and ASD. The clinical spectrum is broad, and most individuals present with mild to moderate ID with or without other syndromic features. Our results suggest that variants in ZNF292 are likely a recurrent cause of a neurodevelopmental disorder manifesting as ID with or without ASD.},
author = {Mirzaa, Ghayda M. and Chong, Jessica X. and Piton, Amélie and Popp, Bernt and Foss, Kimberly and Guo, Hui and Harripaul, Ricardo and Xia, Kun and Scheck, Joshua and Aldinger, Kimberly A. and Sajan, Samin A. and Tang, Sha and Bonneau, Dominique and Beck, Anita and White, Janson and Mahida, Sonal and Harris, Jacqueline and Smith-Hicks, Constance and Hoyer, Juliane and Zweier, Christiane and Reis, André and Thiel, Christian and Jamra, Rami Abou and Zeid, Natasha and Yang, Amy and Farach, Laura S. and Walsh, Laurence and Payne, Katelyn and Rohena, Luis and Velinov, Milen and Ziegler, Alban and Schaefer, Elise and Gatinois, Vincent and Geneviève, David and Simon, Marleen E.H. and Kohler, Jennefer and Rotenberg, Joshua and Wheeler, Patricia and Larson, Austin and Ernst, Michelle E. and Akman, Cigdem I. and Westman, Rachel and Blanchet, Patricia and Schillaci, Lori Anne and Vincent-Delorme, Catherine and Gripp, Karen W. and Mattioli, Francesca and Guyader, Gwenaël Le and Gerard, Bénédicte and Mathieu-Dramard, Michèle and Morin, Gilles and Sasanfar, Roksana and Ayub, Muhammad and Vasli, Nasim and Yang, Sandra and Person, Rick and Monaghan, Kristin G. and Nickerson, Deborah A. and van Binsbergen, Ellen and Enns, Gregory M. and Dries, Annika M. and Rowe, Leah J. and Tsai, Anne C.H. and Svihovec, Shayna and Friedman, Jennifer and Agha, Zehra and Qamar, Raheel and Rodan, Lance H. and Martinez-Agosto, Julian and Ockeloen, Charlotte W. and Vincent, Marie and Sunderland, William James and Bernstein, Jonathan A. and Eichler, Evan E. and Vincent, John B. and Bamshad, Michael J.},
doi = {10.1038/s41436-019-0693-9},
faupublication = {yes},
journal = {Genetics in Medicine},
keywords = {autism spectrum disorders; exome sequencing; intellectual disability; next-generation sequencing; ZNF292},
note = {CRIS-Team Scopus Importer:2019-11-26},
peerreviewed = {Yes},
title = {{De} novo and inherited variants in {ZNF292} underlie a neurodevelopmental disorder with features of autism spectrum disorder},
year = {2019}
}
@article{faucris.230332690,
abstract = {Purpose: To delineate the genotype–phenotype correlation in individuals with likely pathogenic variants in the CLTC gene. Methods: We describe 13 individuals with de novo CLTC variants. Causality of variants was determined by using the tolerance landscape of CLTC and computer-assisted molecular modeling where applicable. Phenotypic abnormalities observed in the individuals identified with missense and in-frame variants were compared with those with nonsense or frameshift variants in CLTC. Results: All de novo variants were judged to be causal. Combining our data with that of 14 previously reported affected individuals (n = 27), all had intellectual disability (ID), ranging from mild to moderate/severe, with or without additional neurologic, behavioral, craniofacial, ophthalmologic, and gastrointestinal features. Microcephaly, hypoplasia of the corpus callosum, and epilepsy were more frequently observed in individuals with missense and in-frame variants than in those with nonsense and frameshift variants. However, this difference was not significant. Conclusions: The wide phenotypic variability associated with likely pathogenic CLTC variants seems to be associated with allelic heterogeneity. The detailed clinical characterization of a larger cohort of individuals with pathogenic CLTC variants is warranted to support the hypothesis that missense and in-frame variants exert a dominant-negative effect, whereas the nonsense and frameshift variants would result in haploinsufficiency.},
author = {Nabais Sá, Maria J. and Venselaar, Hanka and Wiel, Laurens and Trimouille, Aurélien and Lasseaux, Eulalie and Naudion, Sophie and Lacombe, Didier and Piton, Amélie and Vincent-Delorme, Catherine and Zweier, Christiane and Reis, André and Trollmann, Regina and Ruiz, Anna and Gabau, Elisabeth and Vetro, Annalisa and Guerrini, Renzo and Bakhtiari, Somayeh and Kruer, Michael C. and Amor, David J. and Cooper, Monica S. and Bijlsma, Emilia K. and Barakat, Tahsin Stefan and van Dooren, Marieke F. and van Slegtenhorst, Marjon and Pfundt, Rolph and Gilissen, Christian and Willemsen, Michèl A. and de Vries, Bert B.A. and de Brouwer, Arjan P.M. and Koolen, David A.},
doi = {10.1038/s41436-019-0703-y},
faupublication = {yes},
journal = {Genetics in Medicine},
keywords = {CLTC; intellectual disability; neurodevelopmental disorder},
note = {CRIS-Team Scopus Importer:2019-12-10},
peerreviewed = {Yes},
title = {{De} novo {CLTC} variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy},
year = {2019}
}
@article{faucris.267500568,
abstract = {Background High-impact pathogenic variants in more than a thousand genes are involved in Mendelian forms of neurodevelopmental disorders (NDD). Methods This study describes the molecular and clinical characterisation of 28 probands with NDD harbouring heterozygous AGO1 coding variants, occurring de novo for all those whose transmission could have been verified (26/28). Results A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in-frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues. Recurrently identified variants were present in several unrelated individuals: p.(Phe180del), p.(Leu190Pro), p.(Leu190Arg), p.(Gly199Ser), p.(Val254Ile) and p.(Glu376del). AGO1 encodes the Argonaute 1 protein, which functions in gene-silencing pathways mediated by small non-coding RNAs. Three-dimensional protein structure predictions suggest that these variants might alter the flexibility of the AGO1 linker domains, which likely would impair its function in mRNA processing. Affected individuals present with intellectual disability of varying severity, as well as speech and motor delay, autistic behaviour and additional behavioural manifestations. Conclusion Our study establishes that de novo coding variants in AGO1 are involved in a novel monogenic form of NDD, highly similar to the recently reported AGO2-related NDD.},
author = {Schalk, Audrey and Cousin, Margot A. and Challman, Thomas D. and Wain, Karen E. and Powis, Zoe and Minks, Kelly and Trimouille, Aurelien and Lasseaux, Eulalie and Lacombre, Didier and Angelini, Chloe and Michaud, Vincent and Van-Gils, Julien and Spataro, Nino and Ruiz, Anna and Gabau, Elizabeth and Stolerman, Elliot and Washington, Camerun and Louie, Raymond J. and Lanpher, Brendan C. and Kemppainen, Jennifer L. and Innes, A. Micheil and Kooy, R. Frank and Meuwissen, Marije and Goldenberg, Alice and Lecoquierre, Francois and Vera, Gabriella and Diderich, Karin E. M. and Sheidley, Beth Rosen and El Achkar, Christelle Moufawad and Park, Meredith and Hamdan, Fadi F. and Michaud, Jacques L. and Lewis, Ann J. and Zweier, Christiane and Reis, André and Wagner, Matias and Weigand, Heike and Journel, Hubert and Keren, Boris and Passemard, Sandrine and Mignot, Cyril and Van Gassen, Koen L. and Brilstra, Eva H. and Itzikowitz, Gina and O'Heir, Emily and Allen, Jake and Donald, Kirsten A. and Korf, Bruce R. and Skelton, Tammi and Thompson, Michelle L. and Robin, Nathaniel H. and Rudy, Natasha and Dobyns, William B. and Foss, Kimberly and Zarate, Yuri A. and Bosanko, Katherine A. and Alembik, Yves and Durand, Benjamin and Mau-Them, Frederic Tran and Ranza, Emmanuelle and Blanc, Xavier and Antonarakis, Stylianos E. and Mcwalter, Kirsty and Torti, Erin and Millan, Francisca and Dameron, Amy and Tokita, Mari J. and Zimmermann, Michael T. and Klee, Eric W. and Piton, Amelie and Gerard, Benedicte},
doi = {10.1136/jmedgenet-2021-107751},
faupublication = {yes},
journal = {Journal of Medical Genetics},
note = {CRIS-Team WoS Importer:2021-12-24},
peerreviewed = {Yes},
title = {{De} novo coding variants in the {AGO1} gene cause a neurodevelopmental disorder with intellectual disability},
year = {2021}
}
@article{faucris.119543424,
abstract = {Recent studies revealed the power of whole-exome sequencing to identify mutations in sporadic cases with non-syndromic intellectual disability. We now identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay but without any major dysmorphism by trio whole-exome sequencing. Both de novo variants were predicted to be deleterious, and we excluded other variants in this gene. This X-linked gene encodes N-alpha-acetyltransferase 10, the catalytic subunit of the NatA complex involved in multiple cellular processes. A single hypomorphic missense variant p.(Ser37Pro) was previously associated with Ogden syndrome in eight affected males from two different families. This rare disorder is characterized by a highly recognizable phenotype, global developmental delay and results in death during infancy. In an attempt to explain the discrepant phenotype, we used in vitro N-terminal acetylation assays which suggested that the severity of the phenotype correlates with the remaining catalytic activity. The variant in the Ogden syndrome patients exhibited a lower activity than the one seen in the boy with intellectual disability, while the variant in the girl was the most severe exhibiting only residual activity in the acetylation assays used. We propose that N-terminal acetyltransferase deficiency is clinically heterogeneous with the overall catalytic activity determining the phenotypic severity.},
author = {Popp, Bernt and Stove, Svein I. and Endele, Sabine and Myklebust, Line M. and Hoyer, Juliane and Sticht, Heinrich and Azzarello-Burri, Silvia and Rauch, Anita and Arnesen, Thomas and Reis, André},
doi = {10.1038/ejhg.2014.150},
faupublication = {yes},
journal = {European journal of human genetics},
note = {EVALuna2:9247},
pages = {602-9},
peerreviewed = {Yes},
title = {{De} novo missense mutations in the {NAA10} gene cause severe non-syndromic developmental delay in males and females},
volume = {23},
year = {2015}
}
@article{faucris.270404048,
abstract = {Recently, others and we identified de novo FBXO11 (F-Box only protein 11) variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data, our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs.},
author = {Gregor, Anne and Meerbrei, Tanja and Gerstner, Thorsten and Toutain, Annick and Lynch, Sally Ann and Stals, Karen and Maxton, Caroline and Lemke, Johannes R. and Bernat, John A. and Bombei, Hannah M. and Foulds, Nicola and Hunt, David and Kuechler, Alma and Beygo, Jasmin and Stöbe, Petra and Bouman, Arjan and Palomares-Bralo, Maria and Santos-Simarro, Fernando and Garcia-Minaur, Sixto and Pacio-Miguez, Marta and Popp, Bernt and Vasileiou, Georgia and Hebebrand, Moritz and Reis, André and Schuhmann, Sarah and Krumbiegel, Mandy and Brown, Natasha J. and Sparber, Peter and Melikyan, Lyusya and Bessonova, Liudmila and Cherevatova, Tatiana and Sharkov, Artem and Shcherbakova, Natalia and Dabir, Tabib and Kini, Usha and Schwaibold, Eva M.C. and Haack, Tobias B. and Bertoli, Marta and Hoffjan, Sabine and Falb, Ruth and Shinawi, Marwan and Sticht, Heinrich and Zweier, Christiane},
doi = {10.1093/hmg/ddab265},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {CRIS-Team Scopus Importer:2022-03-04},
pages = {440-454},
peerreviewed = {Yes},
title = {{De} novo missense variants in {FBXO11} alter its protein expression and subcellular localization},
volume = {31},
year = {2022}
}
@inproceedings{faucris.228303783,
address = {LONDON},
author = {Straub, Jonas and Konrad, Enrico and Grüner, Johanna and Toutain, A. and Bok, L. A. and Cho, M. T. and Crawford, H. P. and Dubbs, H. and Douglas, G. and Jobling, R. and Johnson, D. and Krock, B. and Mikati, M. A. and Nesbitt, A. and Nicolai, J. and Phillips, M. and Poduri, A. and Ortiz-Gonzales, X. R. and Powis, Z. and Santani, A. and Smith, L. and Stegmann, A. P. A. and Stumpel, C. and Vreeburg, M. and Study, D. D. D. and Fliedner, Anna and Gregor, Anne and Sticht, Heinrich and Zweier, Christiane},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2018-06-16/2018-06-19},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {850-851},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{De} novo missense variants in {RHOBTB2} cause a developmental and epileptic encephalopathy in humans, and altered levels cause neurological defects in {Drosophila}},
venue = {Milan, ITALY},
year = {2019}
}
@article{faucris.109749464,
abstract = {Recently, de novo heterozygous loss-of-function mutations in beta-catenin (CTNNB1) were described for the first time in four individuals with intellectual disability (ID), microcephaly, limited speech and (progressive) spasticity, and functional consequences of CTNNB1 deficiency were characterized in a mouse model. Beta-catenin is a key downstream component of the canonical Wnt signaling pathway. Somatic gain-of-function mutations have already been found in various tumor types, whereas germline loss-of-function mutations in animal models have been shown to influence neuronal development and maturation. We report on 16 additional individuals from 15 families in whom we newly identified de novo loss-of-function CTNNB1 mutations (six nonsense, five frameshift, one missense, two splice mutation, and one whole gene deletion). All patients have ID, motor delay and speech impairment (both mostly severe) and abnormal muscle tone (truncal hypotonia and distal hypertonia/spasticity). The craniofacial phenotype comprised microcephaly (typically -2 to -4 SD) in 12 of 16 and some overlapping facial features in all individuals (broad nasal tip, small alae nasi, long and/or flat philtrum, thin upper lip vermillion). With this detailed phenotypic characterization of 16 additional individuals, we expand and further establish the clinical and mutational spectrum of inactivating CTNNB1 mutations and thereby clinically delineate this new CTNNB1 haploinsufficiency syndrome.},
author = {Kuechler, Alma and Willemsen, Marjolein H. and Albrecht, Beate and Bacino, Carlos A. and Bartholomew, Dennis W. and Van Bokhoven, Hans and Van Den Boogaard, Marie Jose H. and Bramswig, Nuria and Büttner, Christian and Cremer, Kirsten and Czeschik, Johanna Christina and Engels, Hartmut and Van Gassen, Koen and Graf, Elisabeth and Van Haelst, Mieke and He, Weimin and Hogue, Jacob S. and Kempers, Marlies and Koolen, David and Monroe, Glen and De Munnik, Sonja and Pastore, Matthew and Reis, André and Reuter, Miriam and Tegay, David H. and Veltman, Joris and Visser, Gepke and Van Hasselt, Peter and Smeets, Eric E. J. and Vissers, Lisenka and Wieland, Thomas and Wissink, Willemijn and Yntema, Helger and Zink, Alexander Michael and Strom, Tim M. and Luedecke, Hermann-Josef and Kleefstra, Tjitske and Wieczorek, Dagmar},
doi = {10.1007/s00439-014-1498-1},
faupublication = {yes},
journal = {Human genetics},
note = {EVALuna2:9250},
pages = {97-109},
peerreviewed = {Yes},
title = {{De} novo mutations in beta-catenin ({CTNNB1}) appear to be a frequent cause of intellectual disability: expanding the mutational and clinical spectrum},
volume = {134},
year = {2015}
}
@article{faucris.208410806,
abstract = {The etiological spectrum of ultra-rare developmental disorders remains to be fully defined. Chromatin regulatory mechanisms maintain cellular identity and function, where misregulation may lead to developmental defects. Here, we report pathogenic variations in MSL3, which encodes a member of the chromatin-associated male-specific lethal (MSL) complex responsible for bulk histone H4 lysine 16 acetylation (H4K16ac) in flies and mammals. These variants cause an X-linked syndrome affecting both sexes. Clinical features of the syndrome include global developmental delay, progressive gait disturbance, and recognizable facial dysmorphism. MSL3 mutations affect MSL complex assembly and activity, accompanied by a pronounced loss of H4K16ac levels in vivo. Patient-derived cells display global transcriptome alterations of pathways involved in morphogenesis and cell migration. Finally, we use histone deacetylase inhibitors to rebalance acetylation levels, alleviating some of the molecular and cellular phenotypes of patient cells. Taken together, we characterize a syndrome that allowed us to decipher the developmental importance of MSL3 in humans.
},
author = {Basilicata, M. Felicia and Bruel, Ange-Line and Semplicio, Giuseppe and Valsecchi, Claudia Isabelle Keller and Aktas, Tugce and Duffourd, Yannis and Rumpf, Tobias and Morton, Jenny and Bache, Iben and Szymanski, Witold G. and Gilissen, Christian and Vanakker, Olivier and Ounap, Katrin and Mittler, Gerhard and Van Der Burgt, Ineke and El Chehadeh, Salima and Cho, Megan T. and Pfundt, Rolph and Tan, Tiong Yang and Kirchhoff, Maria and Menten, Bjorn and Vergult, Sarah and Lindstrom, Kristin and Reis, André and Johnson, Diana S. and Fryer, Alan and Mckay, Victoria and Fisher, Richard B. and Thauvin-Robinet, Christel and Francis, David and Roscioli, Tony and Pajusalu, Sander and Radtke, Kelly and Ganesh, Jaya and Brunner, Han G. and Wilson, Meredith and Faivre, Laurence and Kalscheuer, Vera M. and Thevenon, Julien and Akhtar, Asifa},
doi = {10.1038/s41588-018-0220-y},
faupublication = {yes},
journal = {Nature Genetics},
note = {EVALuna2:34825},
pages = {1442-1451},
peerreviewed = {Yes},
title = {{De} novo mutations in {MSL3} cause an {X}-linked syndrome marked by impaired histone {H4} lysine 16 acetylation},
volume = {50},
year = {2018}
}
@article{faucris.123944744,
abstract = {An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift mutations and one de novo missense mutation in CTCF in individuals with intellectual disability, microcephaly, and growth retardation. Furthermore, an individual with a larger deletion including CTCF was identified. CTCF (CCCTC-binding factor) is one of the most important chromatin organizers in vertebrates and is involved in various chromatin regulation processes such as higher order of chromatin organization, enhancer function, and maintenance of three-dimensional chromatin structure. Transcriptome analyses in all three individuals with point mutations revealed deregulation of genes involved in signal transduction and emphasized the role of CTCF in enhancer-driven expression of genes. Our findings indicate that haploinsufficiency of CTCF affects genomic interaction of enhancers and their regulated gene promoters that drive developmental processes and cognition.},
author = {Gregor, Anne and Oti, Martin and Kouwenhoven, Evelyn N. and Hoyer, Juliane and Sticht, Heinrich and Ekici, Arif Bülent and Kjaergaard, Susanne and Rauch, Anita and Stunnenberg, Hendrik G. and Uebe, Steffen and Vasileiou, Georgia and Reis, André and Zhou, Huiqing and Zweier, Christiane},
doi = {10.1016/j.ajhg.2013.05.007},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9184},
pages = {124-31},
peerreviewed = {Yes},
title = {{De} novo mutations in the genome organizer {CTCF} cause intellectual disability},
volume = {93},
year = {2013}
}
@article{faucris.246386126,
abstract = {Purpose: MED12 is a subunit of the Mediator multiprotein complex with a central role in RNA polymerase II transcription and regulation of cell growth, development, and differentiation. This might underlie the variable phenotypes in males carrying missense variants in MED12, including X-linked recessive Ohdo, Lujan, and FG syndromes. Methods: By international matchmaking we assembled variant and clinical data on 18 females presenting with variable neurodevelopmental disorders (NDDs) and harboring de novo variants in MED12. Results: Five nonsense variants clustered in the C-terminal region, two splice variants were found in the same exon 8 splice acceptor site, and 11 missense variants were distributed over the gene/protein. Protein truncating variants were associated with a severe, syndromic phenotype consisting of intellectual disability (ID), facial dysmorphism, short stature, skeletal abnormalities, feeding difficulties, and variable other abnormalities. De novo missense variants were associated with a less specific, but homogeneous phenotype including severe ID, autistic features, limited speech and variable other anomalies, overlapping both with females with truncating variants as well as males with missense variants. Conclusion: We establish de novo truncating variants in MED12 as causative for a distinct NDD and de novo missense variants as causative for a severe, less specific NDD in females.},
author = {Polla, D. L. and Bhoj, E. J. and Verheij, J. B.G.M. and Wassink-Ruiter, J. S.Klein and Reis, André and Deshpande, C. and Gregor, Anne and Hill-Karfe, K. and Silfhout, A. T.Vulto van and Pfundt, R. and Bongers, E. M.H.F. and Hakonarson, H. and Berland, S. and Gradek, G. and Banka, S. and Chandler, K. and Gompertz, L. and Huffels, S. C. and Stumpel, C. T.R.M. and Wennekes, R. and Stegmann, A. P.A. and Reardon, W. and Leenders, E. K.S.M. and de Vries, B. B.A. and Li, D. and Zackai, E. and Ragge, N. and Lynch, S. A. and Cuddapah, S. and van Bokhoven, H. and Zweier, Christiane and de Brouwer, A. P.M.},
doi = {10.1038/s41436-020-01040-6},
faupublication = {yes},
journal = {Genetics in Medicine},
note = {CRIS-Team Scopus Importer:2020-12-04},
peerreviewed = {Yes},
title = {{De} novo variants in {MED12} cause {X}-linked syndromic neurodevelopmental disorders in 18 females},
year = {2020}
}
@article{faucris.205567679,
abstract = {Next-generation sequencing combined with international data sharing has enormously facilitated identification of new disease-associated genes and mutations. This is particularly true for genetically extremely heterogeneous entities such as neurodevelopmental disorders (NDDs). Through exome sequencing and world-wide collaborations, we identified and assembled 20 individuals with de novo variants in FBXO11. They present with mild to severe developmental delay associated with a range of features including short (4/20) or tall (2/20) stature, obesity (5/20), microcephaly (4/19) or macrocephaly (2/19), behavioral problems (17/20), seizures (5/20), cleft lip or palate or bifid uvula (3/20), and minor skeletal anomalies. FBXO11 encodes a member of the F-Box protein family, constituting a subunit of an E3-ubiquitin ligase complex. This complex is involved in ubiquitination and proteasomal degradation and thus in controlling critical biological processes by regulating protein turnover. The identified de novo aberrations comprise two large deletions, ten likely gene disrupting variants, and eight missense variants distributed throughout FBXO11. Structural modeling for missense variants located in the CASH or the Zinc-finger UBR domains suggests destabilization of the protein. This, in combination with the observed spectrum and localization of identified variants and the lack of apparent genotype-phenotype correlations, is compatible with loss of function or haploinsufficiency as an underlying mechanism. We implicate de novo missense and likely gene disrupting variants in FBXO11 in a neurodevelopmental disorder with variable intellectual disability and various other features.
},
author = {Gregor, Anne and Sadleir, Lynette G. and Asadollahi, Reza and Azzarello-Burri, Silvia and Battaglia, Agatino and Ousager, Lilian Bomme and Boonsawat, Paranchai and Bruel, Ange-Line and Buchert, Rebecca and Calpena, Eduardo and Cogne, Benjamin and Dallapiccola, Bruno and Distelmaier, Felix and Elmslie, Frances and Faivre, Laurence and Haack, Tobias B. and Harrison, Victoria and Henderson, Alex and Hunt, David and Isidor, Bertrand and Joset, Pascal and Kumada, Satoko and Lachmeijer, Augusta M. A. and Lees, Melissa and Lynch, Sally Ann and Martinez, Francisco and Matsumoto, Naomichi and Mcdougall, Carey and Mefford, Heather C. and Miyake, Noriko and Myers, Candace T. and Moutton, Sebastien and Nesbitt, Addie and Novelli, Antonio and Orellana, Carmen and Rauch, Anita and Rosello, Monica and Saida, Ken and Santani, Avni B. and Sarkar, Ajoy and Scheffer, Ingrid E. and Shinawi, Marwan and Steindl, Katharina and Symonds, Joseph D. and Zackai, Elaine H. and Univ, Washington Ctr Mendelian Genomics D. D. D. and Reis, André and Sticht, Heinrich and Zweier, Christiane},
doi = {10.1016/j.ajhg.2018.07.003},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:34619},
pages = {305-316},
peerreviewed = {Yes},
title = {{De} {Novo} {Variants} in the {F}-{Box} {Protein} {FBXO11} in 20 {Individuals} with a {Variable} {Neurodevelopmental} {Disorder}},
volume = {103},
year = {2018}
}
@article{faucris.319724791,
abstract = {The disconnected (disco)-interacting protein 2 (DIP2) gene was first identified in D. melanogaster and contains a DNA methyltransferase-associated protein 1 (DMAP1) binding domain, Acyl-CoA synthetase domain and AMP-binding sites. DIP2 regulates axonal bifurcation of the mushroom body neurons in D. melanogaster and is required for axonal regeneration in the neurons of C. elegans. The DIP2 homologues in vertebrates, Disco-interacting protein 2 homolog A (DIP2A), Disco-interacting protein 2 homolog B (DIP2B), and Disco-interacting protein 2 homolog C (DIP2C), are highly conserved and expressed widely in the central nervous system. Although there is evidence that DIP2C plays a role in cognition, reports of pathogenic variants in these genes are rare and their significance is uncertain. We present 23 individuals with heterozygous DIP2C variants, all manifesting developmental delays that primarily affect expressive language and speech articulation. Eight patients had de novo variants predicting loss-of-function in the DIP2C gene, two patients had de novo missense variants, three had paternally inherited loss of function variants and six had maternally inherited loss-of-function variants, while inheritance was unknown for four variants. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects, and bicuspid aortic valve). Minor facial anomalies were inconsistent but included a high anterior hairline with a long forehead, broad nasal tip, and ear anomalies. Brainspan analysis showed elevated DIP2C expression in the human neocortex at 10–24 weeks after conception. With the cases presented herein, we provide phenotypic and genotypic data supporting the association between loss-of-function variants in DIP2C with a neurocognitive phenotype.},
author = {Ha, Thoa and Morgan, Angela and Bartos, Meghan N. and Beatty, Katelyn and Cogné, Benjamin and Braun, Dominique and Gerber, Céline B. and Gaspar, Harald and Kopps, Anna M. and Rieubland, Claudine and Hurst, Anna C.E. and Amor, David J. and Nizon, Mathilde and Pasquier, Laurent and Pfundt, Rolph and Reis, André and Siu, Victoria Mok and Tessarech, Marine and Thompson, Michelle L. and Vincent, Marie and de Vries, Bert B.A. and Walsh, Matthew B. and Wechsler, Stephanie Burns and Zweier, Christiane and Schnur, Rhonda E. and Guillen Sacoto, Maria J. and Margot, Henri and Masotto, Barbara and Palafoll, Maria Irene Valenzuela and Nawaz, Urwah and Voineagu, Irina and Slavotinek, Anne},
doi = {10.1002/ajmg.a.63559},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
keywords = {developmental delay; DIP2; DIP2C; intellectual disability; speech articulation; speech delay},
note = {CRIS-Team Scopus Importer:2024-03-15},
peerreviewed = {Yes},
title = {{De} novo variants predicting haploinsufficiency for {DIP2C} are associated with expressive speech delay},
year = {2024}
}
@article{faucris.109485024,
abstract = {Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8(+) memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.},
author = {Bowes, John and Budu-Aggrey, Ashley and Hüffmeier, Ulrike and Uebe, Steffen and Steel, Kathryn and Hebert, Harry L. and Wallace, Chris and Massey, Jonathan and Bruce, Ian N. and Bluett, James and Feletar, Marie and Morgan, Ann W. and Marzo-Ortega, Helena and Donohoe, Gary and Morris, Derek W. and Helliwell, Philip and Ryan, Anthony W. and Kane, David and Warren, Richard B. and Korendowych, Eleanor and Alenius, Gerd-Marie and Giardina, Emiliano and Packham, Jonathan and Mcmanus, Ross and Fitzgerald, Oliver and Mchugh, Neil and Brown, Matthew A. and Ho, Pauline and Behrens, Frank and Burkhardt, Harald and Reis, André and Barton, Anne},
doi = {10.1038/ncomms7046},
faupublication = {yes},
journal = {Nature Communications},
note = {EVALuna2:9282},
pages = {6046},
peerreviewed = {Yes},
title = {{Dense} genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis},
volume = {6},
year = {2015}
}
@article{faucris.286399663,
abstract = {Neuronal heterogeneity has been established as a pillar of higher central nervous system function, but glial heterogeneity and its implications for neural circuit function are poorly understood. Here we show that the adult mouse dentate gyrus (DG) of the hippocampus is populated by molecularly distinct astrocyte subtypes that are associated with distinct DG layers. Astrocytes localized to different DG compartments also exhibit subtype-specific morphologies. Physiologically, astrocytes in upper DG layers form large syncytia, while those in lower DG compartments form smaller networks. Astrocyte subtypes differentially express glutamate transporters, which is associated with different amplitudes of glutamate transporter-mediated currents. Key molecular and morphological features of astrocyte diversity in the mice DG are conserved in humans. This adds another layer of complexity to our understanding of brain network composition and function, which will be crucial for further studies on astrocytes in health and disease.},
author = {Karpf, Julian and Unichenko, Petr and Chalmers, Nicholas and Beyer, Felix and Wittmann, Marie-Theres and Schneider, Julia and Fidan, Elif and Reis, André and Beckervordersandforth, Jan and Brandner, Sebastian and Liebner, Stefan and Falk, Sven and Sagner, Andreas and Henneberger, Christian and Beckervordersandforth, Ruth},
doi = {10.1038/s41593-022-01192-5},
faupublication = {yes},
journal = {Nature Neuroscience},
note = {CRIS-Team Scopus Importer:2022-12-09},
pages = {1626-1638},
peerreviewed = {Yes},
title = {{Dentate} gyrus astrocytes exhibit layer-specific molecular, morphological and physiological features},
volume = {25},
year = {2022}
}
@article{faucris.285404372,
abstract = {The human genome contains more than one million tandem repeats (TRs), DNA sequences containing multiple approximate copies of a motif repeated contiguously. TRs account for significant genetic variation, with 50 + diseases attributed to changes in motif number. A few diseases have been to be caused by small indels in variable number tandem repeats (VNTRs) including poly-cystic kidney disease type 1 (MCKD1) and monogenic type 1 diabetes. However, small indels in VNTRs are largely unexplored mainly due to the long and complex structure of VNTRs with multiple motifs. We developed a method, code-adVNTR, that utilizes multi-motif hidden Markov models to detect both, motif count variation and small indels, within VNTRs. In simulated data, code-adVNTR outperformed GATK-HaplotypeCaller in calling small indels within large VNTRs. We used code-adVNTR to characterize coding VNTRs in the 1000 genomes data identifying many population-specific variants, and to reliably call MUC1 mutations for MCKD1.},
author = {Park, Jonghun and Bakhtiari, Mehrdad and Popp, Bernt and Wiesener, Michael and Bafna, Vineet},
doi = {10.1016/j.isci.2022.104785},
faupublication = {yes},
journal = {iScience},
keywords = {Genetics; Genomics; Human genetics; Molecular genetics},
note = {CRIS-Team Scopus Importer:2022-11-18},
peerreviewed = {Yes},
title = {{Detecting} tandem repeat variants in coding regions using code-{adVNTR}},
volume = {25},
year = {2022}
}
@inproceedings{faucris.248094796,
address = {LONDON},
author = {Hebebrand, Moritz and Thiel, C. T. and Kraus, Cornelia and Ekici, Arif Bülent and Reis, André and Zweier, Christiane},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {340-340},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Detection} rate and re-analysis of exome sequencing data in a cohort of 207 individuals with neurodevelopmental disorders},
year = {2020}
}
@article{faucris.316123984,
abstract = {Molecular Tumor Boards (MTBs) converge state-of-the-art next-generation sequencing (NGS) methods with the expertise of an interdisciplinary team consisting of clinicians, pathologists, human geneticists, and molecular biologists to provide molecularly informed guidance in clinical decision making to the treating physician. In the present study, we particularly focused on elucidating the factors impacting on the clinical translation of MTB recommendations, utilizing data generated from gene panel mediated comprehensive genomic profiling (CGP) of 554 patients at the MTB of the Comprehensive Cancer Center Erlangen, Germany, during the years 2016 to 2020. A subgroup analysis of cases with available follow-up data (n = 332) revealed 139 cases with a molecularly informed MTB recommendation, which was successfully implemented in the clinic in 44 (31.7%) of these cases. Here, the molecularly matched treatment was applied in 45.4% (n = 20/44) of cases for ≥6 months and in 25% (n = 11/44) of cases for 12 months or longer (median time to treatment failure, TTF: 5 months, min: 1 month, max: 38 months, ongoing at data cut-off). In general, recommendations were preferentially implemented in the clinic when of high (i.e., tier 1) clinical evidence level. In particular, this was the case for MTB recommendations suggesting the application of PARP, PIK3CA, and IDH1/2 inhibitors. The main reason for non-compliance to the MTB recommendation was either the application of non-matched treatment modalities (n = 30)/stable disease (n = 7), or deteriorating patient condition (n = 22)/death of patient (n = 9). In summary, this study provides an insight into the factors affecting the clinical implementation of molecularly informed MTB recommendations, and careful considerations of these factors may guide future processes of clinical decision making.},
author = {Tögel, Lars and Schubart, Christoph and Lettmaier, Sebastian and Neufert, Clemens and Hoyer, Juliane and Wolff, Kerstin and Moskalev, Evgeny and Stöhr, Robert and Agaimy, Abbas and Wiesmann da Silva Reis, André and Wullich, Bernd and Mackensen, Andreas and Pavel, Marianne Ellen and Beckmann, Matthias and Hartmann, Arndt and Fietkau, Rainer and Meidenbauer, Norbert and Haller, Florian and Spörl, Silvia},
doi = {10.3390/cancers15245892},
faupublication = {yes},
journal = {Cancers},
keywords = {Molecular Tumor Board; clinical decision making; precision medicine; molecular pathology; real-world data; cancer care},
note = {EVALuna2:545872},
peerreviewed = {Yes},
title = {{Determinants} {Affecting} the {Clinical} {Implementation} of a {Molecularly} {Informed} {Molecular} {Tumor} {Board} {Recommendation}: {Experience} from a {Tertiary} {Cancer} {Center}.},
volume = {15},
year = {2023}
}
@article{faucris.229371633,
abstract = {In genetic diagnostics, the path goes from single-gene testing to gene-panel analyses, especially for rare genetic diseases. In July 2016, an amendment to the EBM (Einheitlicher Bewertungsmaßstab, Regulations on Fees for Statutory Health Insurance) introduced the possibility of performing genetic analyses using next-generation sequencing (NGS) on patients with rare diseases. However, the mutation search in a sequence encoding more than 25 kilobases (kb) was subject to approval by the health insurance funds and was further restricted over time by a billing exclusion for a previous analysis of individual genes of less than 25 kb. We report from the diagnostic laboratories of the Bavarian State Association of the BVDH (Berufsverband Deutscher Humangenetiker e. V.) on the experiences we have gained with the application procedures, the objections, the approval rate, the reasons for rejection and the diagnostic outcome in the analysis of large gene panels for various rare disorders. In the survey period of seven quarters, a total of 314 applications were prepared in four diagnostic laboratories to justify an application according to GOP (Gebührenordnungsposition, fee schedule position) 11514, all of which were reviewed by the MDK (Medizinischer Dienst der Krankenkassen; Medical Service to Health Insurance Funds). 71% of the applications were rejected. A total of 95 applications (29%) were approved, but in some cases only after up to five objections. The rejections were based on both socio-medical and formal criteria, whereby in most cases a therapeutic relevance considered to be lacking was used as a socio-medical argument. The approved comprehensive NGS analyses made it possible to make a genetic diagnosis in more than 30% of the patients examined, which was relevant to treatment in two thirds of the cases. In summary, the conditional approval of an NGS analysis according to GOP 11514 and the resulting obstacles hinder the medically necessary and useful diagnostics in the care of patients with rare diseases.},
author = {Abicht, Angela and Neuhann, Teresa and Mehnert, Laura and Rost, Imma and Wiesmann da Silva Reis, André and Zweier, Christiane and Holinski-Feder, Elke},
doi = {10.1007/s11825-019-00258-3},
faupublication = {yes},
journal = {Medizinische Genetik},
keywords = {Application procedure “large panel”; Gene panel; Panel diagnostics; Scale of charges position 11514; Uniform assessment benchmark},
note = {CRIS-Team Scopus Importer:2019-11-19},
peerreviewed = {unknown},
title = {{Diagnostics} of rare diseases with next generation sequencing—arrived at the patients or rejected? {Diagnostik} seltener {Erkrankungen} mit „next generation sequencing“ – angekommen oder abgewehrt?},
year = {2019}
}
@article{faucris.119673444,
abstract = {Autosomal recessive inherited neurodevelopmental disorders are highly heterogeneous, and many, possibly most, of the disease genes are still unknown.To promote the identification of disease genes through confirmation of previously described genes and presentation of novel candidates and provide an overview of the diagnostic yield of exome sequencing in consanguineous families.Autozygosity mapping in families and exome sequencing of index patients were performed in 152 consanguineous families (the parents descended from a same ancestor) with at least 1 offspring with intellectual disability (ID). The study was conducted from July 1, 2008, to June 30, 2015, and data analysis was conducted from July 1, 2015, to August 31, 2016.Of the 152 consanguineous families enrolled, 1 child (in 45 families [29.6%]) or multiple children (107 families [70.4%]) had ID; additional features were present in 140 of the families (92.1%). The mean (SD) age of the children was 10.3 (9.0) years, and 171 of 297 (57.6%) were male. In 109 families (71.7%), potentially protein-disrupting and clinically relevant variants were identified. Of these, a clear clinical genetic diagnosis was made in 56 families (36.8%) owing to 57 (likely) pathogenic variants in 50 genes already established in neurodevelopmental disorders (46 autosomal recessive, 2 X-linked, and 2 de novo) or in 7 previously proposed recessive candidates. In 5 of these families, potentially treatable disorders were diagnosed (mutations in PAH, CBS, MTHFR, CYP27A1, and HIBCH), and in 1 family, 2 disease-causing homozygous variants in different genes were identified. In another 48 families (31.6%), 52 convincing recessive variants in candidate genes that were not previously reported in regard to neurodevelopmental disorders were identified. Of these, 14 were homozygous and truncating in GRM7, STX1A, CCAR2, EEF1D, GALNT2, SLC44A1, LRRIQ3, AMZ2, CLMN, SEC23IP, INIP, NARG2, FAM234B, and TRAP1. The diagnostic yield was higher in individuals with severe ID (35 of 77 [45.5%]), in multiplex families (42 of 107 [39.3%]), in patients with additional features (30 of 70 [42.9%]), and in those with remotely related parents (15 of 34 [44.1%]).Because of the high diagnostic yield of 36.8% and the possibility of identifying treatable diseases or the coexistence of several disease-causing variants, using exome sequencing as a first-line diagnostic approach in consanguineous families with neurodevelopmental disorders is recommended. Furthermore, the literature is enriched with 52 convincing candidate genes that are awaiting confirmation in independent families.},
author = {Reuter, Miriam and Tawamie, Hasan and Buchert, Rebecca and Gebril, Ola Hosny and Froukh, Tawfiq and Thiel, Christian and Uebe, Steffen and Ekici, Arif Bülent and Krumbiegel, Mandy and Zweier, Christiane and Hoyer, Juliane and Eberlein, Karolin and Bauer, Judith and Scheller, Ute and Strom, Tim M. and Hoffjan, Sabine and Abdelraouf, Ehab R. and Meguid, Nagwa A. and Abboud, Ahmad and Al Khateeb, Mohammed Ayman and Fakher, Mahmoud and Hamdan, Saber and Ismael, Amina and Muhammad, Safia and Abdallah, Ebtessam and Sticht, Heinrich and Wieczorek, Dagmar and Reis, André and Abou Jamra, Rami},
doi = {10.1001/jamapsychiatry.2016.3798},
faupublication = {yes},
journal = {JAMA Psychiatry},
note = {EVALuna2:9388},
pages = {293-299},
peerreviewed = {Yes},
title = {{Diagnostic} {Yield} and {Novel} {Candidate} {Genes} by {Exome} {Sequencing} in 152 {Consanguineous} {Families} {With} {Neurodevelopmental} {Disorders}},
volume = {74},
year = {2017}
}
@article{faucris.315106064,
abstract = {Background and Aims: The anti-MAdCAM-1 antibody ontamalimab demonstrated efficacy in a phase II trial in ulcerative colitis and results of early terminated phase III trials are pending, but its precise mechanisms of action are still unclear. Thus, we explored the mechanisms of action of ontamalimab and compared it to the anti-α4β7 antibody vedolizumab. Methods: We studied MAdCAM-1 expression with RNA sequencing and immunohistochemistry. The mechanisms of action of ontamalimab were assessed with fluorescence microscopy, dynamic adhesion and rolling assays. We performed in vivo cell trafficking studies in mice and compared ontamalimab and vedolizumab surrogate [-s] antibodies in experimental models of colitis and wound healing. We analysed immune cell infiltration under anti-MAdCAM-1 and anti-α4β7 treatment by single-cell transcriptomics and studied compensatory trafficking pathways. Results: MAdCAM-1 expression was increased in active inflammatory bowel disease. Binding of ontamalimab to MAdCAM-1 induced the internalization of the complex. Functionally, ontamalimab blocked T cell adhesion similar to vedolizumab, but also inhibited L-selectin-dependent rolling of innate and adaptive immune cells. Despite conserved mechanisms in mice, the impact of ontamalimab-s and vedolizumab-s on experimental colitis and wound healing was similar. Single-cell RNA sequencing demonstrated enrichment of ontamalimab-s-treated lamina propria cells in specific clusters, and in vitro experiments indicated that redundant adhesion pathways are active in these cells. Conclusions: Ontamalimab has unique and broader mechanisms of action compared to vedolizumab. However, this seems to be compensated for by redundant cell trafficking circuits and leads to similar preclinical efficacy of anti-α4β7 and anti-MAdCAM-1 treatment. These results will be important for the interpretation of pending phase III data.},
author = {Schulze, Lisa and Becker, Emily and Dedden, Mark and Liu, Lijuan and Van Passen, Chiara and Mohamed Abdou, Mariam and Müller, Tanja and Wiendl, Maximilian and Ullrich, Karen and Atreya, Imke and Leppkes, Moritz and Ekici, Arif Bülent and Kirchner, Philipp and Stürzl, Michael and Sexton, Dan and Palliser, Deborah and Atreya, Raja and Siegmund, Britta and Neurath, Markus and Zundler, Sebastian},
doi = {10.1093/ecco-jcc/jjad088},
faupublication = {yes},
journal = {Journal of Crohns & Colitis},
note = {CRIS-Team Scopus Importer:2023-12-15},
pages = {1817-1832},
peerreviewed = {Yes},
title = {{Differential} {Effects} of {Ontamalimab} {Versus} {Vedolizumab} on {Immune} {Cell} {Trafficking} in {Intestinal} {Inflammation} and {Inflammatory} {Bowel} {Disease}},
volume = {17},
year = {2023}
}
@article{faucris.272554295,
abstract = {The transcription factor FOXG1 serves pleiotropic functions in brain development ranging from the regulation of precursor proliferation to the control of cortical circuit formation. Loss-of-function mutations and duplications of FOXG1 are associated with neurodevelopmental disorders in humans illustrating the importance of FOXG1 dosage for brain development. Aberrant FOXG1 dosage has been found to disrupt the balanced activity of glutamatergic and GABAergic neurons, but the underlying mechanisms are not fully understood. We report that FOXG1 is expressed in the main adult neurogenic niches in mice, i.e. the hippocampal dentate gyrus and the subependymal zone/olfactory bulb system, where neurogenesis of glutamatergic and GABAergic neurons persists into adulthood. These niches displayed differential vulnerability to increased FOXG1 dosage: high FOXG1 levels severely compromised survival and glutamatergic dentate granule neuron fate acquisition in the hippocampal neurogenic niche, but left neurogenesis of GABAergic neurons in the subependymal zone/olfactory bulb system unaffected. Comparative transcriptomic analyses revealed a significantly higher expression of the apoptosis-linked nuclear receptor Nr4a1 in FOXG1-overexpressing hippocampal neural precursors. Strikingly, pharmacological interference with NR4A1 function rescued FOXG1-dependent death of hippocampal progenitors. Our results reveal differential vulnerability of neuronal subtypes to increased FOXG1 dosage and suggest that activity of a FOXG1/NR4A1 axis contributes to such subtype-specific response.},
author = {Schäffner, Iris and Wittmann, Marie-Theres and Vogel, Tanja and Lie, Dieter Chichung},
doi = {10.1038/s41380-022-01497-8},
faupublication = {yes},
journal = {Molecular Psychiatry},
note = {CRIS-Team WoS Importer:2022-04-08},
peerreviewed = {Yes},
title = {{Differential} vulnerability of adult neurogenic niches to dosage of the neurodevelopmental-disorder linked gene {Foxg1}},
year = {2022}
}
@article{faucris.293798079,
abstract = {The MAPT gene, encoding the microtubule-associated protein tau on chromosome 17q21.31, is result of an inversion polymorphism, leading to two allelic variants (H1 and H2). Homozygosity for the more common haplotype H1 is associated with an increased risk for several tauopathies, but also for the synucleinopathy Parkinson’s disease (PD). In the present study, we aimed to clarify whether the MAPT haplotype influences expression of MAPT and SNCA, encoding the protein α-synuclein (α-syn), on mRNA and protein levels in postmortem brains of PD patients and controls. We also investigated mRNA expression of several other MAPT haplotype-encoded genes. Postmortem tissues from cortex of fusiform gyrus (ctx-fg) and of the cerebellar hemisphere (ctx-cbl) of neuropathologically confirmed PD patients (n = 95) and age- and sex-matched controls (n = 81) were MAPT haplotype genotyped to identify cases homozygous for either H1 or H2. Relative expression of genes was quantified using real-time qPCR; soluble and insoluble protein levels of tau and α-syn were determined by Western blotting. Homozygosity for H1 versus H2 was associated with increased total MAPT mRNA expression in ctx-fg regardless of disease state. Inversely, H2 homozygosity was associated with markedly increased expression of the corresponding antisense MAPT-AS1 in ctx-cbl. PD patients had higher levels of insoluble 0N3R and 1N4R tau isoforms regardless of the MAPT genotype. The increased presence of insoluble α-syn in PD patients in ctx-fg validated the selected postmortem brain tissue. Our findings in this small, but well controlled cohort of PD and controls support a putative biological relevance of tau in PD. However, we did not identify any link between the disease-predisposing H1/H1 associated overexpression of MAPT with PD status. Further studies are required to gain a deeper understanding of the potential regulatory role of MAPT-AS1 and its association to the disease-protective H2/H2 condition in the context of PD.},
author = {Tauber, Christina V. and Schwarz, Sigrid C. and Rösler, Thomas W. and Arzberger, Thomas and Gentleman, Steve and Windl, Otto and Krumbiegel, Mandy and Reis, André and Ruf, Viktoria C. and Herms, Jochen and Höglinger, Günter U.},
doi = {10.1186/s40478-023-01534-9},
faupublication = {yes},
journal = {Acta Neuropathologica Communications},
keywords = {Gene expression; H1 and H2 haplotype; MAPT; Parkinson’s disease; Postmortem human brain; Protein level; Synucleins; Tau protein},
note = {CRIS-Team Scopus Importer:2023-03-24},
peerreviewed = {Yes},
title = {{Different} {MAPT} haplotypes influence expression of total {MAPT} in postmortem brain tissue},
volume = {11},
year = {2023}
}
@article{faucris.276339387,
abstract = {Purpose: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes. Methods: Clinical data was collected through an extensive web-based survey. Results: We included 44 patients with a variant in a CSS-associated gene and a prenatal phenotype; 9 of these patients have been reported before. Prenatal anomalies that were frequently observed in our cohort include hydrocephalus, agenesis of the corpus callosum, hypoplastic left heart syndrome, persistent left vena cava, diaphragmatic hernia, renal agenesis, and intrauterine growth restriction. Anal anomalies were frequently identified after birth in patients with ARID1A variants (6/14, 43%). Interestingly, pathogenic ARID1A variants were much more frequently identified in the current prenatal cohort (16/44, 36%) than in postnatal CSS cohorts (5%-9%). Conclusion: Our data shed new light on the prenatal phenotype of patients with pathogenic variants in CSS genes.},
author = {van der Sluijs, Pleuntje J. and Joosten, Marieke and Alby, Caroline and Attié-Bitach, Tania and Gilmore, Kelly and Dubourg, Christele and Fradin, Mélanie and Wang, Tianyun and Kurtz-Nelson, Evangeline C. and Ahlers, Kaitlyn P. and Arts, Peer and Barnett, Christopher P. and Ashfaq, Myla and Baban, Anwar and van den Born, Myrthe and Borrie, Sarah and Busa, Tiffany and Byrne, Alicia and Carriero, Miriam and Cesario, Claudia and Chong, Karen and Cueto-González, Anna Maria and Dempsey, Jennifer C. and Diderich, Karin E.M. and Doherty, Dan and Farholt, Stense and Gerkes, Erica H. and Gorokhova, Svetlana and Govaerts, Lutgarde C.P. and Gregersen, Pernille A. and Hickey, Scott E. and Lefebvre, Mathilde and Mari, Francesca and Martinovic, Jelena and Northrup, Hope and O'Leary, Melanie and Parbhoo, Kareesma and Patrier, Sophie and Popp, Bernt and Santos-Simarro, Fernando and Stoltenburg, Corinna and Thauvin-Robinet, Christel and Thompson, Elisabeth and Vulto-van Silfhout, Anneke T. and Zahir, Farah R. and Scott, Hamish S. and Earl, Rachel K. and Eichler, Evan E. and Vora, Neeta L. and Wilnai, Yael and Giordano, Jessica L. and Wapner, Ronald J. and Rosenfeld, Jill A. and Haak, Monique C. and Santen, Gijs W.E.},
doi = {10.1016/j.gim.2022.04.010},
faupublication = {yes},
journal = {Genetics in Medicine},
keywords = {ARID1A; ARID1B BAFopathy; BAF-complex; Fetal; SMARCA4; SMARCB1},
note = {CRIS-Team Scopus Importer:2022-06-03},
peerreviewed = {Yes},
title = {{Discovering} a new part of the phenotypic spectrum of {Coffin}-{Siris} syndrome in a fetal cohort},
year = {2022}
}
@incollection{faucris.230838637,
abstract = {Human pluripotent stem (PS) cells are a relevant platform to model human-specific neurological disorders. In this chapter, we focus on human stem cell models for neuropsychiatric disorders including induced pluripotent stem (iPS) cell-derived neural precursor cells (NPCs), neurons and cerebral organoids. We discuss crucial steps for planning human disease modeling experiments. We introduce the different strategies of human disease modeling including transdifferentiation, human embryonic stem (ES) cell-based models, iPS cell-based models and genome editing options. Analysis of disease-relevant phenotypes is discussed. In more detail, we provide exemplary insight into modeling of the neurodevelopmental defects in autism spectrum disorder (ASD) and the process of neurodegeneration in Alzheimer's disease (AD). Besides monogenic diseases, iPS cell-derived models also generated data from idiopathic and sporadic cases.},
author = {Kaindl, Johanna and Winner, Beate},
booktitle = {Behavioral Neurogenomics},
doi = {10.1007/7854{\_}2019{\_}111},
editor = {Elisabeth B. Binder, Torsten Klengel},
faupublication = {yes},
keywords = {Disease modeling; hiPSC-derived neurons; hiPSCs; Neuropsychiatric disorders; Organoids},
note = {CRIS-Team Scopus Importer:2019-12-24},
pages = {159-183},
peerreviewed = {unknown},
series = {Current Topics in Behavioral Neurosciences},
title = {{Disease} {Modeling} of {Neuropsychiatric} {Brain} {Disorders} {Using} {Human} {Stem} {Cell}-{Based} {Neural} {Models}},
volume = {42},
year = {2019}
}
@article{faucris.252999821,
abstract = {Purpose: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.},
author = {Harris, Holly K. and Nakayama, Tojo and Lai, Jenny and Zhao, Boxun and Argyrou, Nikoleta and Gubbels, Cynthia S. and Soucy, Aubrie and Genetti, Casie A. and Suslovitch, Victoria and Rodan, Lance H. and Tiller, George E. and Lesca, Gaetan and Gripp, Karen W. and Asadollahi, Reza and Hamosh, Ada and Applegate, Carolyn D. and Turnpenny, Peter D. and Simon, Marleen E. H. and Volker-Touw, Catharina M. L. and Gassen, Koen L. I. Van and Binsbergen, Ellen Van and Pfundt, Rolph and Gardeitchik, Thatjana and Vries, Bert B. A. De and Immken, Ladonna L. and Buchanan, Catherine and Willing, Marcia and Toler, Tomi L. and Fassi, Emily and Baker, Laura and Vansenne, Fleur and Wang, Xiadong and Ambrus, Julian L. and Fannemel, Madeleine and Posey, Jennifer E. and Agolini, Emanuele and Novelli, Antonio and Rauch, Anita and Boonsawat, Paranchai and Fagerberg, Christina R. and Larsen, Martin J. and Kibaek, Maria and Labalme, Audrey and Poisson, Alice and Payne, Katelyn K. and Walsh, Laurence E. and Aldinger, Kimberly A. and Balciuniene, Jorune and Skraban, Cara and Gray, Christopher and Murrell, Jill and Bupp, Caleb P. and Pascolini, Giulia and Grammatico, Paola and Broly, Martin and Kury, Sebastien and Nizon, Mathilde and Rasool, Iqra Ghulam and Zahoor, Muhammad Yasir and Kraus, Cornelia and Reis, André and Iqbal, Muhammad and Uguen, Kevin and Audebert-Bellanger, Severine and Ferec, Claude and Redon, Sylvia and Baker, Janice and Wu, Yunhong and Zampino, Guiseppe and Syrbe, Steffan and Brosse, Ines and Jamra, Rami Abou and Dobyns, William B. and Cohen, Lilian L. and Blomhoff, Anne and Mignot, Cyril and Keren, Boris and Courtin, Thomas and Agrawal, Pankaj B. and Beggs, Alan H. and Yu, Timothy W.},
doi = {10.1038/s41436-021-01114-z},
faupublication = {yes},
journal = {Genetics in Medicine},
note = {CRIS-Team Scopus Importer:2021-03-26},
peerreviewed = {Yes},
title = {{Disruption} of {RFX} family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior},
year = {2021}
}
@article{faucris.217942596,
abstract = {Background: Several subunits of the SWI/SNF chromatin remodeling complex are implicated in both cancer and neurodevelopmental disorders (NDD). Though there is no clinical evidence for an increased tumor risk in individuals with NDDs due to germline mutations in most of these genes so far, this has been repeatedly proposed and discussed. A young woman with NDD due to a de novo mutation in ARID1B now presented with a large renal (> 19 cm in diameter) and multiple hepatic angiomyolipomas (AMLs) but no other signs of tuberous sclerosis complex. Methods: We analyzed tumor and healthy tissue samples with exome and panel sequencing. Results: Additionally to the previously known, germline ARID1B variant we identified a post-zygotic truncating TSC2 variant in both renal and hepatic AMLs but not in any of the healthy tissues. We did not detect any further, obvious tumor driver events. The identification of a passenger variant in SIPA1L3 in both AMLs points to a common clonal origin. Metastasis of the renal AML into the liver is unlikely on the basis of discordant histopathological features. Our findings therefore point to very low-grade mosaicism for the TSC2 variant, possibly in a yet unknown mesenchymal precursor cell that expanded clonally during tumor development. A possible contribution of the germline ARID1B variant to the tumorigenesis remains unclear but cannot be excluded given the absence of any other evident tumor drivers in the AMLs. Conclusion: This unique case highlights the blurred line between tumor genetics and post-zygotic events that can complicate exact molecular diagnoses in patients with rare manifestations. It also demonstrates the relevance of multiple disorders in a single individual, the challenges of detecting low-grade mosaicisms, and the importance of proper diagnosis for treatment and surveillance.},
author = {Popp, Bernt and Agaimy, Abbas and Kraus, Cornelia and Knaup, Karl and Ekici, Arif Bülent and Uebe, Steffen and Reis, André and Wiesener, Michael and Zweier, Christiane},
doi = {10.1186/s12885-019-5633-1},
faupublication = {yes},
journal = {BMC Cancer},
keywords = {Angiomyolipoma; ARID1B; Mosaic; Neurodevelopmental disorders; TSC2; Tuberous sclerosis complex},
note = {CRIS-Team Scopus Importer:2019-05-21},
peerreviewed = {Yes},
title = {{Dissecting} {TSC2}-mutated renal and hepatic angiomyolipomas in an individual with {ARID1B}-associated intellectual disability},
volume = {19},
year = {2019}
}
@article{faucris.123417184,
abstract = {While adult neurogenesis is considered to be restricted to the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ), recent studies in humans and rodents provide evidence for newly generated neurons in regions generally considered as non-neurogenic, e.g., the striatum. Stimulating dopaminergic neurotransmission has the potential to enhance adult neurogenesis in the SVZ and the DG most likely via D2/D3 dopamine (DA) receptors. Here, we investigated the effect of two distinct preferential D2/D3 DA agonists, Pramipexole (PPX), and Ropinirole (ROP), on adult neurogenesis in the hippocampus and striatum of adult naïve mice. To determine newly generated cells in the DG incorporating 5-bromo-2'-deoxyuridine (BrdU) a proliferation paradigm was performed in which two BrdU injections (100 mg/kg) were applied intraperitoneally within 12 h after a 14-days-DA agonist treatment. Interestingly, PPX, but not ROP significantly enhanced the proliferation in the DG by 42% compared to phosphate buffered saline (PBS)-injected control mice. To analyze the proportion of newly generated cells differentiating into mature neurons, we quantified cells co-expressing BrdU and Neuronal Nuclei (NeuN) 32 days after the last of five BrdU injections (50 mg/kg) applied at the beginning of 14-days DA agonist or PBS administration. Again, PPX only enhanced neurogenesis in the DG significantly compared to ROP- and PBS-injected mice. Moreover, we explored the pro-neurogenic effect of both DA agonists in the striatum by quantifying neuroblasts expressing doublecortin (DCX) in the entire striatum, as well as in the dorsal and ventral sub-regions separately. We observed a significantly higher number of DCX(+) neuroblasts in the dorsal compared to the ventral sub-region of the striatum in PPX-injected mice. These results suggest that the stimulation of hippocampal and dorsal striatal neurogenesis may be up-regulated by PPX. The increased generation of neural cells, both in constitutively active and quiescent neurogenic niches, might be related to the proportional higher D3 receptor affinity of PPX, non-dopaminergic effects of PPX, or altered motor behavior.},
author = {Salvi, Rachele and Steigleder, Tobias and Schlachetzki, Johannes and Waldmann, Elisabeth and Schwab, Stefan and Winner, Beate and Winkler, Jürgen and Kohl, Zacharias},
doi = {10.3389/fnins.2016.00077},
faupublication = {yes},
journal = {Frontiers in Neuroscience},
note = {EVALuna2:5538},
pages = {77},
peerreviewed = {Yes},
title = {{Distinct} {Effects} of {Chronic} {Dopaminergic} {Stimulation} on {Hippocampal} {Neurogenesis} and {Striatal} {Doublecortin} {Expression} in {Adult} {Mice}},
volume = {10},
year = {2016}
}
@article{faucris.277817265,
abstract = {Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is caused by mutations in one of at least five genes and leads to kidney failure usually in mid adulthood. Throughout the literature, variable numbers of families have been reported, where no mutation can be found and therefore termed ADTKD-not otherwise specified. Here, we aim to clarify the genetic cause of their diseases in our ADTKD registry. Sequencing for all known ADTKD genes was performed, followed by SNaPshot minisequencing for the dupC (an additional cytosine within a stretch of seven cytosines) mutation of MUC1. A virtual panel containing 560 genes reported in the context of kidney disease (nephrome) and exome sequencing were then analyzed sequentially. Variants were validated and tested for segregation. In 29 of the 45 registry families, mutations in known ADTKD genes were found, mostly in MUC1. Sixteen families could then be termed ADTKD-not otherwise specified, of which nine showed diagnostic variants in the nephrome (four in COL4A5, two in INF2 and one each in COL4A4, PAX2, SALL1 and PKD2). In the other seven families, exome sequencing analysis yielded potential disease associated variants in novel candidate genes for ADTKD; evaluated by database analyses and genome-wide association studies. For the great majority of our ADTKD registry we were able to reach a molecular genetic diagnosis. However, a small number of families are indeed affected by diseases classically described as a glomerular entity. Thus, incomplete clinical phenotyping and atypical clinical presentation may have led to the classification of ADTKD. The identified novel candidate genes by exome sequencing will require further functional validation.},
author = {Wopperer, Florian and Knaup, Karl and Stanzick, Kira J. and Schneider, Karen and Jobst-Schwan, Tilman and Ekici, Arif Bülent and Uebe, Steffen and Wenzel, Andrea and Schliep, Stefan and Schürfeld, Carsten and Seitz, Randolf and Bernhardt, Wanja and Gödel, Markus and Wiesener, Antje and Popp, Bernt and Stark, Klaus J. and Gröne, Hermann Josef and Friedrich, Björn and Weiß, Martin and Basic-Jukic, Nikolina and Schiffer, Mario and Schröppel, Bernd and Huettel, Bruno and Beck, Bodo B. and Sayer, John A. and Ziegler, Christine and Büttner-Herold, Maike and Amann, Kerstin Ute and Heid, Iris M. and Wiesmann da Silva Reis, André and Pasutto, Francesca and Wiesener, Michael},
doi = {10.1016/j.kint.2022.04.031},
faupublication = {yes},
journal = {Kidney International},
keywords = {ADTKD; Alport syndrome; exome; MITKD; MUC1; UMOD},
note = {CRIS-Team Scopus Importer:2022-07-15},
peerreviewed = {Yes},
title = {{Diverse} molecular causes of unsolved autosomal dominant tubulointerstitial kidney diseases},
year = {2022}
}
@article{faucris.251066747,
abstract = {Purpose: Postsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants. Methods: The clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing. Results: The clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit–hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies. Conclusion: The present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy. [Figure not available: see fulltext.]},
author = {Rodriguez-Palmero, Agusti and Boerrigter, Melissa Maria and Gomez-Andres, David and Aldinger, Kimberly A. and Marcos-Alcalde, Inigo and Popp, Bernt and Everman, David B. and Lovgren, Alysia Kern and Arpin, Stephanie and Bahrambeigi, Vahid and Beunders, Gea and Bisgaard, Anne-Marie and Bjerregaard, V. A. and Bruel, Ange-Line and Challman, Thomas D. and Cogne, Benjamin and Coubes, Christine and De Man, Stella A. and Denomme-Pichon, Anne-Sophie and Dye, Thomas J. and Elmslie, Frances and Feuk, Lars and Garcia-Minaur, Sixto and Gertler, Tracy and Giorgio, Elisa and Gruchy, Nicolas and Haack, Tobias B. and Haldeman-Englert, Chad R. and Haukanes, Bjorn Ivar and Hoyer, Juliane and Hurst, Anna C. E. and Isidor, Bertrand and Soller, Maria Johansson and Kushary, Sulagna and Kvarnung, Malin and Landau, Yuval E. and Leppig, Kathleen A. and Lindstrand, Anna and Kleinendorst, Lotte and Mackenzie, Alex and Mandrile, Giorgia and Mendelsohn, Bryce A. and Moghadasi, Setareh and Morton, Jenny E. and Moutton, Sebastien and Mueller, Amelie J. and O'Leary, Melanie and Pacio-Miguez, Marta and Palomares-Bralo, Maria and Parikh, Sumit and Pfundt, Rolph and Pode-Shakked, Ben and Rauch, Anita and Repnikova, Elena and Revah-Politi, Anya and Ross, Meredith J. and Ruivenkamp, Claudia A. L. and Sarrazin, Elisabeth and Savatt, Juliann M. and Schlueter, Agatha and Schoenewolf-Greulich, Bitten and Shad, Zohra and Shaw-Smith, Charles and Shieh, Joseph T. and Shohat, Motti and Spranger, Stephanie and Thiese, Heidi and Mau-Them, Frederic Tran and Van Bon, Bregje and Van De Burgt, Ineke and Van De Laar, Ingrid M. B. H. and Van Drie, Esmee and Van Haelst, Mieke M. and Van Ravenswaaij-Arts, Conny M. and Verdura, Edgard and Vitobello, Antonio and Waldmueller, Stephan and Whiting, Sharon and Zweier, Christiane and Prada, Carlos E. and De Vries, Bert B. A. and Dobyns, William B. and Reiter, Simone F. and Gomez-Puertas, Paulino and Pujol, Aurora and Tumer, Zeynep},
doi = {10.1038/s41436-020-01075-9},
faupublication = {yes},
journal = {Genetics in Medicine},
note = {CRIS-Team Scopus Importer:2021-03-05},
peerreviewed = {Yes},
title = {{DLG4}-related synaptopathy: a new rare brain disorder},
year = {2021}
}
@article{faucris.123135804,
abstract = {Nonmotor symptoms of cognitive and affective nature are present in premotor and motor stages of Parkinson's disease (PD). Neurogenesis, the generation of new neurons, persists throughout the mammalian life span in the hippocampal dentate gyrus. Adult hippocampal neurogenesis may be severely affected in the course of PD, accounting for some of the neuropsychiatric symptoms such as depression and cognitive impairment. Two important PD-related pathogenic factors have separately been attributed to contribute to both PD and adult hippocampal neurogenesis: dopamine depletion and accumulation of alpha-synuclein (alpha-syn). In the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model, altered neurogenesis has been linked merely to a reduced dopamine level. Here, we seek to determine whether a distinct endogenous alpha-syn expression pattern is associated, possibly contributing to the hippocampal neurogenic deficit. We observed a persistent reduction of striatal dopamine and a loss of tyrosine hydroxylase-expressing neurons in the substantia nigra pars compacta in contrast to a complete recovery of tyrosine hydroxylase-immunoreactive dopaminergic fibers within the striatum. However, dopamine levels in the hippocampus were significantly decreased. Survival of newly generated neurons was significantly reduced and paralleled by an accumulation of truncated, membrane-associated, insoluble alpha-syn within the hippocampus. Specifically, the presence of truncated alpha-syn species was accompanied by increased activity of calpain-1, a calcium-dependent protease. Our results further substantiate the broad effects of dopamine loss in PD-susceptible brain nuclei, gradually involved in the PD course. Our findings also indicate a detrimental synergistic interplay between dopamine depletion and posttranslational modification of alpha-syn, contributing to impaired hippocampal plasticity in PD. (C) 2015 Wiley Periodicals, Inc.},
author = {Schlachetzki, Johannes and Grimm, Thomas and Schlachetzki, Zinayida and Ben Abdallah, Nada M. B. and Ettle, Benjamin and Voehringer, Patrizia and Ferger, Boris and Winner, Beate and Nuber, Silke and Winkler, Jürgen},
doi = {10.1002/jnr.23677},
faupublication = {yes},
journal = {Journal of Neuroscience Research},
keywords = {MPTP;C-terminal-cleaved alpha-synuclein;calpain-1},
month = {Jan},
note = {EVALuna2:25336},
pages = {62-73},
peerreviewed = {Yes},
title = {{Dopaminergic} lesioning impairs adult hippocampal neurogenesis by distinct modification of α-synuclein},
volume = {94},
year = {2016}
}
@article{faucris.120556304,
abstract = {Williams-Beuren syndrome (WBS) is a relatively common, clinically recognizable microdeletion syndrome. In most cases the typical heterozygous deletion of 1.5 Mb on chromosome 7q11.23 spanning about 26 genes can be identified. Also some larger or smaller atypical deletions have been reported and associated with additional or atypical phenotypic aspects. We report on an individual with typical WBS due to the common deletion and with refractory infantile spasms. Using trio-exome sequencing, we identified a de novo truncating variant c.1200del, p (Lys401Serfs*25) in GABRA1 as the likely cause of the early onset epilepsy. This unique case not only allows to further define the phenotypic spectrum of infantile epileptic encephalopathy associated with rare de novo GABRA1 variants but exemplifies the need for a sensitive review of unclear associations in clinically defined syndromes and for extended diagnostic work-up in individuals with unusual presentations of a genetically confirmed diagnosis.},
author = {Popp, Bernt and Trollmann, Regina and Büttner, Christian and Caliebe, Almuth and Thiel, Christian and Hüffmeier, Ulrike and Reis, André and Zweier, Christiane},
doi = {10.1016/j.ejmg.2016.09.002},
faupublication = {yes},
journal = {European Journal of Medical Genetics},
note = {EVALuna2:9310},
pages = {549-53},
peerreviewed = {Yes},
title = {{Do} the exome: {A} case of {Williams}-{Beuren} syndrome with severe epilepsy due to a truncating de novo variant in {GABRA1}},
volume = {59},
year = {2016}
}
@article{faucris.284124322,
abstract = {Complex genetic predispositions accelerate the chronic degeneration of midbrain substantia nigra neurons in Parkinson’s disease (PD). Deciphering the human molecular makeup of PD pathophysiology can guide the discovery of therapeutics to slow the disease progression. However, insights from human postmortem brain studies only portray the latter stages of PD, and there is a lack of data surrounding molecular events preceding the neuronal loss in patients. We address this gap by identifying the gene dysregulation of live midbrain neurons reprogrammed in vitro from the skin cells of 42 individuals, including sporadic and familial PD patients and matched healthy controls. To minimize bias resulting from neuronal reprogramming and RNA-seq methods, we developed an analysis pipeline integrating PD transcriptomes from different RNA-seq datasets (unsorted and sorted bulk vs. single-cell and Patch-seq) and reprogramming strategies (induced pluripotency vs. direct conversion). This PD cohort’s transcriptome is enriched for human genes associated with known clinical phenotypes of PD, regulation of locomotion, bradykinesia and rigidity. Dysregulated gene expression emerges strongest in pathways underlying synaptic transmission, metabolism, intracellular trafficking, neural morphogenesis and cellular stress/immune responses. We confirmed a synaptic impairment with patch-clamping and identified pesticides and endoplasmic reticulum stressors as the most significant gene-chemical interactions in PD. Subsequently, we associated the PD transcriptomic profile with candidate pharmaceuticals in a large database and a registry of current clinical trials. This study highlights human transcriptomic pathways that can be targeted therapeutically before the irreversible neuronal loss. Furthermore, it demonstrates the preclinical relevance of unbiased large transcriptomic assays of reprogrammed patient neurons.},
author = {van den Hurk, Mark and Lau, Shong and Marchetto, Maria C. and Mertens, Jerome and Stern, Shani and Corti, Olga and Brice, Alexis and Winner, Beate and Winkler, Jürgen and Gage, Fred H. and Bardy, Cedric},
doi = {10.1038/s41531-022-00400-0},
faupublication = {yes},
journal = {npj Parkinson’s Disease},
note = {CRIS-Team Scopus Importer:2022-10-28},
pages = {134},
peerreviewed = {Yes},
title = {{Druggable} transcriptomic pathways revealed in {Parkinson}’s patient-derived midbrain neurons},
volume = {8},
year = {2022}
}
@inproceedings{faucris.230819002,
author = {Montalbano, Antonino and Juergensen, Lonny and Fukami, Maki and Thiel, Christian and Hauer, Nadine and Fricke-Otto, Susanne and Binder, Gerhard and Naiki, Y. and Ogata, Tsutomu and Hassel, David and Rappold, Gudrun A.},
faupublication = {yes},
note = {EVALuna2:34829},
pages = {425-425},
peerreviewed = {Yes},
title = {{Dual} {Function} of the {Retinoic} {Acid} {Catabolizing} {Enzyme} {CYP26C1}-{Underlying} {Idiopathic} {Short} {Stature} and {Modifying} {Disease} {Severity} in {SHOX} {Deficiency}},
volume = {90},
year = {2018}
}
@inproceedings{faucris.208416935,
author = {Killy, Barbara and Huber, Angelika and Ekici, Arif Bülent and Wirtz, Stefan and Dalpke, A. and Lang, Roland},
faupublication = {yes},
note = {EVALuna2:33888},
pages = {194-194},
peerreviewed = {Yes},
title = {{Dual} role of the mycobacterial cord factor {TDM} in cross-regulation of macrophage responses to {IFN} gamma},
volume = {47},
year = {2017}
}
@article{faucris.107516684,
author = {Rohde, Doris and Schmitt, Heike and Winterpacht, Andreas and Münster, Tino},
doi = {10.1097/EJA.0000000000000053},
faupublication = {yes},
journal = {European Journal of Anaesthesiology},
note = {EVALuna2:9224},
pages = {341-2},
peerreviewed = {Yes},
title = {{Duchenne} muscular dystrophy and malignant hyperthermia: a genetic study of the ryanodine receptor in 47 patients},
volume = {31},
year = {2014}
}
@article{faucris.124122724,
abstract = {Skeletal ciliopathies are a heterogeneous group of autosomal recessive osteochondrodysplasias caused by defects in formation, maintenance and function of the primary cilium. Mutations in the underlying genes affect the molecular motors, intraflagellar transport complexes (IFT), or the basal body. The more severe phenotypes are caused by defects of genes of the dynein-2 complex, where mutations in DYNC2H1, WDR34 and WDR60 have been identified. In a patient with a Jeune-like phenotype we performed exome sequencing and identified compound heterozygous missense and nonsense mutations in DYNC2LI1 segregating with the phenotype. DYNC2LI1 is ubiquitously expressed and interacts with DYNC2H1 to form the dynein-2 complex important for retrograde IFT. Using DYNC2LI1 siRNA knockdown in fibroblasts we identified a significantly reduced cilia length proposed to affect cilia function. In addition, depletion of DYNC2LI1 induced altered cilia morphology with broadened ciliary tips and accumulation of IFT-B complex proteins in accordance with retrograde IFT defects. Our results expand the clinical spectrum of ciliopathies caused by defects of the dynein-2 complex.},
author = {Keßler, Kristin and Wunderlich, Ina and Uebe, Steffen and Falk, Nathalie and Gießl, Andreas and Brandstätter, Johann Helmut and Popp, Bernt and Klinger, Patricia and Ekici, Arif Bülent and Sticht, Heinrich and Dörr, Helmuth-Günther and Reis, André and Roepman, Ronald and Seemanova, Eva and Thiel, Christian},
doi = {10.1038/srep11649},
faupublication = {yes},
journal = {Scientific Reports},
note = {EVALuna2:9281},
pages = {11649},
peerreviewed = {Yes},
title = {{DYNC2LI1} mutations broaden the clinical spectrum of dynein-2 defects},
volume = {5},
year = {2015}
}
@article{faucris.107221224,
abstract = {Hereditary spastic paraplegias are a group of inherited motor neuron diseases characterized by progressive paraparesis and spasticity. Mutations in the spastic paraplegia gene SPG11, encoding spatacsin, cause an autosomal-recessive disease trait; however, the precise knowledge about the role of spatacsin in neurons is very limited. We for the first time analyzed the expression and function of spatacsin in human forebrain neurons derived from human pluripotent stem cells including lines from two SPG11 patients and two controls. SPG11 patients'-derived neurons exhibited downregulation of specific axonal-related genes, decreased neurite complexity and accumulation of membranous bodies within axonal processes. Altogether, these data point towards axonal pathologies in human neurons with SPG11 mutations. To further corroborate spatacsin function, we investigated human pluripotent stem cell-derived neurons and mouse cortical neurons. In these cells, spatacsin was located in axons and dendrites. It colocalized with cytoskeletal and synaptic vesicle (SV) markers and was present in synaptosomes. Knockdown of spatacsin in mouse cortical neurons evidenced that the loss of function of spatacsin leads to axonal instability by downregulation of acetylated tubulin. Finally, time-lapse assays performed in SPG11 patients'-derived neurons and spatacsin-silenced mouse neurons highlighted a reduction in the anterograde vesicle trafficking indicative of impaired axonal transport. By employing SPG11 patient-derived forebrain neurons and mouse cortical neurons, this study provides the first evidence that SPG11 is implicated in axonal maintenance and cargo trafficking. Understanding the cellular functions of spatacsin will allow deciphering mechanisms of motor cortex dysfunction in autosomal-recessive hereditary spastic paraplegia.},
author = {Perez-Branguli, Francesc and Mishra, Himanshu Kumar and Prots, Iryna and Havlicek, Steven and Kohl, Zacharias and Saul, Domenica and Rummel, Christine and Dorca-Arevalo, Jonatan and Regensburger, Martin and Graef, Daniela and Sock, Elisabeth and Blasi, Juan and Groemer, Teja W. and Schlötzer-Schrehardt, Ursula and Winkler, Jürgen and Winner, Beate},
doi = {10.1093/hmg/ddu200},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:4956},
pages = {4859-74},
peerreviewed = {Yes},
title = {{Dysfunction} of spatacsin leads to axonal pathology in {SPG11}-linked hereditary spastic paraplegia},
volume = {23},
year = {2014}
}
@article{faucris.247442462,
abstract = {PPP2R5D-related neurodevelopmental disorder (NDD) is a rare autosomal-dominant disease with developmental delay and mild to severe intellectual disability. So far, fewer than 30 affected individuals with mostly recurrent, de novo missense variants in PPP2R5D were reported. Recently, parkinsonism with an onset between 20 and 40 years was reported in four adult individuals with the same p.(Glu200Lys) variant in PPP2R5D. By trio exome sequencing we now identified the variant p.(Glu198Lys) in a 29 year old woman presenting with typical clinical manifestations of PPP2R5D-related neurodevelopmental disorder and additionally with motor decline and levodopa responsive, early-onset parkinsonism from her mid-twenties on. Accordingly, a clear reduction of dopamine transporter in the striatum on both sides was revealed by brain scintigraphy. Our findings further expand the molecular and clinical spectrum of PPP2R5D-related NDD and confirm the association with parkinsonism in early adulthood. This has marked implications for prognosis of PPP2R5D-related NDDs and for the therapeutic management of motor decline and parkinson-like symptoms in affected individuals.},
author = {Hetzelt, Katalin and Kerling, Frank and Kraus, Cornelia and Rauch, Christophe and Thiel, Christian and Winterholler, Martin and Reis, André and Zweier, Christiane},
doi = {10.1016/j.ejmg.2020.104123},
faupublication = {yes},
journal = {European Journal of Medical Genetics},
keywords = {Neurodevelopmental disorder; Parkinson's disease; Parkinsonism; PPP2R5D},
month = {Jan},
note = {CRIS-Team Scopus Importer:2021-01-01},
peerreviewed = {Yes},
title = {{Early}-onset parkinsonism in {PPP2R5D}-related neurodevelopmental disorder},
volume = {64},
year = {2021}
}
@article{faucris.274117205,
author = {Zunke, Friederike and Winner, Beate and Richter, Franziska and Caraveo, Gabriela},
doi = {10.3389/fcell.2021.752378},
faupublication = {yes},
journal = {Frontiers in Cell and Developmental Biology},
keywords = {alpha-synuclein; lysosomes; neurodegeneration; protein misfolding; spread; synucleinopathies},
note = {CRIS-Team Scopus Importer:2021-10-08},
peerreviewed = {Yes},
title = {{Editorial}: {Intracellular} {Mechanisms} of α-{Synuclein} {Processing}.},
volume = {9},
year = {2021}
}
@article{faucris.205196749,
abstract = {Background and aims: Despite proven clinical efficacy of vedolizumab (VDZ) for inducing and maintaining remission in patients with Crohn's disease (CD) and ulcerative colitis (UC), subgroups of patients have no therapeutic benefit from anti-α4β7 integrin therapy with VDZ. Within this study, we aimed to identify genetic, cellular, and immunological mechanisms that define response and failure to VDZ treatment.
Methods: Intestinal RNA sequencing was performed in UC and CD patients before and at week 14 of VDZ therapy. α4β7 expression on peripheral and mucosal immune cells was assessed by flow cytometry and immunohistochemistry. Cellular modes of VDZ-mediated action were analyzed ex vivo and in VDZ-treated inflammatory bowel disease patients.
Results: Transcriptome analysis showed an impairment of signaling cascades associated with adhesion, diapedesis, and migration of granulocytes and agranulocytes upon VDZ therapy. In non-remitters to VDZ therapy, a tissue destructive and leukocyte-mediated inflammatory activity with activation of TNF-dependent pathways was present, all of which were inhibited in remitters to VDZ. Clinical remission was associated with a significant reduction of α4β7 expression on Th2 and Th17 polarized mucosal CD4+ T cells at week 14 of VDZ therapy and with significantly higher numbers of α4β7-expressing mucosal cells prior to the initiation of VDZ therapy compared with non-remitters.
Conclusion: Intestinal α4β7 expression prior to VDZ therapy might represent a biomarker that predicts therapeutic response to subsequent VDZ treatment. Due to high activation of TNF signaling in VDZ non-remitters, anti-TNF treatment might represent a promising therapeutic strategy in VDZ refractory patients.},
author = {Rath, Timo and Billmeier, Ulrike and Ferrazzi, Fulvia and Ekici, Arif Bülent and Neurath, Markus and Atreya, Raja and Vieth, Michael},
doi = {10.3389/fimmu.2018.01700},
faupublication = {yes},
journal = {Frontiers in Immunology},
note = {EVALuna2:34622},
peerreviewed = {Yes},
title = {{Effects} of {Anti}-{Integrin} {Treatment} {With} {Vedolizumab} on {Immune} {Pathways} and {Cytokines} in {Inflammatory} {Bowel} {Diseases}},
volume = {9},
year = {2018}
}
@article{faucris.273930855,
abstract = {Current protocols converting human induced pluripotent stem cells (iPSCs) into induced microglia-like cells (iMGL) are either dependent on overexpression of transcription factors or require substantial experience in stem-cell technologies. Here, we developed an easy-to-use two-step protocol to convert iPSCs into functional iMGL via: (1) highly efficient differentiation of hematopoietic progenitor cells (HPCs) from iPSCs, and (2) optimized maturation of HPCs to iMGL. A sequential harvesting approach led to an increased HPC yield. The protocol implemented a freezing step, thus allowing HPC biobanking and flexible timing of differentiation into iMGL. Our iMGL responded adequately to the inflammatory stimuli LPS, and iMGL RNAseq analysis matched those of other frequently used protocols. Comparing three different coating modalities, we increased the iMGL yield by culturing on uncoated glass surfaces, thereby retaining differentiation efficiency and functional hallmarks of iMGL. In summary, we provide a high-quality, easy-to-use protocol, rendering generation and functional studies on iMGL an accessible lab resource.},
author = {Lanfer, Jonas and Winner, Beate and Kaindl, Johanna and Krumm, Laura and Acera, Miguel Gonzalez and Neurath, Markus and Regensburger, Martin and Krach, Florian},
doi = {10.3390/ijms23094526},
faupublication = {yes},
journal = {International Journal of Molecular Sciences},
keywords = {cell differentiation; immunology; microglia; neurology; pluripotent stem cells},
note = {CRIS-Team Scopus Importer:2022-04-29},
peerreviewed = {Yes},
title = {{Efficient} and {Easy} {Conversion} of {Human} {iPSCs} into {Functional} {Induced} {Microglia}-like {Cells}},
url = {https://www.mdpi.com/1422-0067/23/9/4526},
volume = {23},
year = {2022}
}
@article{faucris.110839124,
abstract = {In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with β-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.},
author = {Mielenz, Dirk and Reichel, Martin and Jia, T. and Quinlan, E. B. and Stöckl, Thomas and Mettang, M. and Zilske, Daniel and Kirmizi Alsan, Elif and Schoenberger, P. and Praetner, M. and Huber, Sabine and Amato, Davide and Schwarz, Martin and Purohit, P. and Brachs, Sebastian and Spranger, J. and Heß, Andreas and Büttner, Christian and Ekici, Arif Bülent and Perez-Branguli, F. and Winner, Beate and Rauschenberger, Verena and Banaschewski, T. and Bokde, A. L. W. and Buechel, C. and Conrod, P. J. and Desrivieres, Sylvane and Flor, Herta and Frouin, V. and Gallinat, J. and Garavan, H. and Gowland, P. and Heinz, A. and Martinot, J-L and Lemaitre, H. and Nees, F. and Paus, T. and Smolka, M. N. and Schambony, Alexandra and Bäuerle, Tobias and Eulenburg, Volker and Alzheimer, Christian and Lourdusamy, A. and Schumann, G. and Müller, Christian P.},
doi = {10.1038/mp.2017.63},
faupublication = {yes},
journal = {Molecular Psychiatry},
note = {EVALuna2:4036},
pages = {1303-1319},
peerreviewed = {Yes},
title = {{EFhd2}/{Swiprosin}-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction},
volume = {23},
year = {2017}
}
@article{faucris.253927922,
abstract = {Background: An identical homozygous missense variant in EIF3F, identified through a large-scale genome-wide sequencing approach, was reported as causative in nine individuals with a neurodevelopmental disorder, characterized by variable intellectual disability, epilepsy, behavioral problems and sensorineural hearing-loss. To refine the phenotypic and molecular spectrum of EIF3F-related neurodevelopmental disorder, we examined independent patients. Results: 21 patients were homozygous and one compound heterozygous for c.694T>G/p.(Phe232Val) in EIF3F. Haplotype analyses in 15 families suggested that c.694T>G/p.(Phe232Val) was a founder variant. All affected individuals had developmental delays including delayed speech development. About half of the affected individuals had behavioral problems, altered muscular tone, hearing loss, and short stature. Moreover, this study suggests that microcephaly, reduced sensitivity to pain, cleft lip/palate, gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum. Minor dysmorphic features were observed, although neither the individuals’ facial nor general appearance were obviously distinctive. Symptoms in the compound heterozygous individual with an additional truncating variant were at the severe end of the spectrum in regard to motor milestones, speech delay, organic problems and pre- and postnatal growth of body and head, suggesting some genotype–phenotype correlation. Conclusions: Our study refines the phenotypic and expands the molecular spectrum of EIF3F-related syndromic neurodevelopmental disorder.},
author = {Hüffmeier, Ulrike and Kraus, Cornelia and Reuter, Miriam and Uebe, Steffen and Abbott, Mary-Alice and Ahmed, Syed A. and Rawson, Kristyn L. and Barr, Eileen and Li, Hong and Bruel, Ange-Line and Faivre, Laurence and Mau-Them, Frederic Tran and Botti, Christina and Brooks, Susan and Burns, Kaitlyn and Ward, D. Isum and Dutra-Clarke, Marina and Martinez-Agosto, Julian A. and Lee, Hane and Nelson, Stanley F. and Zacher, Pia and Abou Jamra, Rami and Kloeckner, Chiara and Mcgaughran, Julie and Kohlhase, Juergen and Schuhmann, Sarah and Moran, Ellen and Pappas, John and Raas-Rothschild, Annick and Sacoto, Maria J. Guillen and Henderson, Lindsay B. and Palculict, Timothy Blake and Mullegama, Sureni and Elloumi, Houda Zghal and Reich, Adi and Vergano, Samantha A. Schrier and Wahl, Erica and Reis, André and Zweier, Christiane},
doi = {10.1186/s13023-021-01744-1},
faupublication = {yes},
journal = {Orphanet Journal of Rare Diseases},
keywords = {Altered muscular tone; Behavioral difficulties; Deafness; EIF3F gene; Neurodevelopmental disorder; Short stature},
note = {CRIS-Team Scopus Importer:2021-04-02},
peerreviewed = {Yes},
title = {{EIF3F}-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum},
volume = {16},
year = {2021}
}
@inproceedings{faucris.274483726,
address = {LONDON},
author = {Hüffmeier, Ulrike and Kraus, Cornelia and Reuter, Miriam and Uebe, Steffen and Abbott, Mary-Alice and Ahmed, Syed A. and Rawson, Kristyn L. and Barr, Eileen and Li, Hong and Bruel, Ange-Line and Faivre, Laurence and Them, Frederic Tran Mau and Botti, Christina and Brooks, Susan and Brooks, Susan and Burns, Kaitlyn and Ward, Isum and Dutra-Clarke, Marina and Martinez-Agosto, Julian A. and Lee, Hane and Nelson, Stanley F. and Zacher, Pia and Abou Jamra, Rami and Kloeckner, Chiara and Mcgaughran, Julie and Kohlhase, Juergen and Schuhmann, Sarah and Moran, Ellen and Pappas, John and Raas-Rothschild, Annick and Sacoto, Maria J. Guillen and Henderson, Lindsay B. and Palculict, Timothy Blake and Mullegama, Sureni V. and Elloumi, Houda Zghal and Reich, Adi and Vergano, Samantha A. Schrier and Wahl, Erica and Reis, André and Zweier, Christiane},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
doi = {10.1186/s13023-021-01744-1},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2022-05-06},
pages = {246-247},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{EIF3F}-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum},
year = {2022}
}
@article{faucris.106340564,
abstract = {Heterozygous copy number variants (CNVs) or sequence variants in the contactin-associated protein 2 gene CNTNAP2 have been discussed as risk factors for a wide spectrum of neurodevelopmental and neuropsychiatric disorders. Bi-allelic aberrations in this gene are causative for an autosomal-recessive disorder with epilepsy, severe intellectual disability (ID) and cortical dysplasia (CDFES). As the number of reported individuals is still limited, we aimed at a further characterisation of the full mutational and clinical spectrum.Targeted sequencing, chromosomal microarray analysis or multigene panel sequencing was performed in individuals with severe ID and epilepsy.We identified homozygous mutations, compound heterozygous CNVs or CNVs and mutations in CNTNAP2 in eight individuals from six unrelated families. All aberrations were inherited from healthy, heterozygous parents and are predicted to be deleterious for protein function. Epilepsy occurred in all affected individuals with onset in the first 3.5 years of life. Further common aspects were ID (severe in 6/8), regression of speech development (5/8) and behavioural anomalies (7/8). Interestingly, cognitive impairment in one of two affected brothers was, in comparison, relatively mild with good speech and simple writing abilities. Cortical dysplasia that was previously reported in CDFES was not present in MRIs of six individuals and only suspected in one.By identifying novel homozygous or compound heterozygous, deleterious CNVs and mutations in eight individuals from six unrelated families with moderate-to-severe ID, early onset epilepsy and behavioural anomalies, we considerably broaden the mutational and clinical spectrum associated with bi-allelic aberrations in CNTNAP2.},
author = {Smogavec, Mateja and Cleall, Alison and Hoyer, Juliane and Lederer, Damien and Nassogne, Marie-Cecile and Palmer, Elizabeth E. and Deprez, Marie and Benoit, Valerie and Maystadt, Isabelle and Noakes, Charlotte and Leal-Esquivel, Alejandro and Shaw, Marie and Gecz, Jozef and Raymond, Lucy and Reis, André and Shears, Deborah and Brockmann, Knut and Zweier, Christiane},
doi = {10.1136/jmedgenet-2016-103880},
faupublication = {yes},
journal = {Journal of Medical Genetics},
note = {EVALuna2:9347},
pages = {820-827},
peerreviewed = {Yes},
title = {{Eight} further individuals with intellectual disability and epilepsy carrying bi-allelic {CNTNAP2} aberrations allow delineation of the mutational and phenotypic spectrum},
volume = {53},
year = {2016}
}
@article{faucris.222412708,
abstract = {Objective To analyze clinical phenotypes associated with KCNC1 variants other than the Progressive Myoclonus Epilepsy-causing variant p.Arg320His, determine the electrophysiological functional impact of identified variants and explore genotype-phenotype-physiological correlations. Methods Ten cases with putative pathogenic variants in KCNC1 were studied. Variants had been identified via whole-exome sequencing or gene panel testing. Clinical phenotypic data were analyzed. To determine functional impact of variants detected in the K(v)3.1 channel encoded by KCNC1, Xenopus laevis oocyte expression system and automated two-electrode voltage clamping were used. Results Six unrelated patients had a Developmental and Epileptic Encephalopathy and a recurrent de novo variant p.Ala421Val (c.1262C > T). Functional analysis of p.Ala421Val revealed loss of function through a significant reduction in whole-cell current, but no dominant-negative effect. Three patients had a contrasting phenotype of Developmental Encephalopathy without seizures and different KCNC1 variants, all of which caused loss of function with reduced whole-cell currents. Evaluation of the variant p.Ala513Val (c.1538C > T) in the tenth case, suggested it was a variant of uncertain significance. Interpretation These are the first reported cases of Developmental and Epileptic Encephalopathy due to KCNC1 mutation. The spectrum of phenotypes associated with KCNC1 is now broadened to include not only a Progressive Myoclonus Epilepsy, but an infantile onset Developmental and Epileptic Encephalopathy, as well as Developmental Encephalopathy without seizures. Loss of function is a key feature, but definitive electrophysiological separation of these phenotypes has not yet emerged.},
author = {Cameron, Jillian M. and Maljevic, Snezana and Nair, Umesh and Aung, Ye Htet and Cogne, Benjamin and Bezieau, Stephane and Blair, Edward and Isidor, Bertrand and Zweier, Christiane and Reis, André and Koenig, Mary Kay and Maarup, Timothy and Sarco, Dean and Afenjar, Alexandra and Huq, A. H. M. Mahbubul and Kukolich, Mary and De Villemeur, Thierry Billette and Nava, Caroline and Heron, Benedicte and Petrou, Steven and Berkovic, Samuel F.},
doi = {10.1002/acn3.50822},
faupublication = {yes},
journal = {Annals of Clinical and Translational Neurology},
note = {CRIS-Team WoS Importer:2019-07-16},
peerreviewed = {Yes},
title = {{Encephalopathies} with {KCNC1} variants: genotype-phenotype-functional correlations},
year = {2019}
}
@article{faucris.106348264,
abstract = {Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (P<5 × 10(-8)). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.},
author = {Tsoi, Lam C. and Spain, Sarah L. and Ellinghaus, Eva and Stuart, Philip E. and Capon, Francesca and Knight, Jo and Tejasvi, Trilokraj and Kang, Hyun M. and Allen, Michael H. and Lambert, Sylviane and Stoll, Stefan W. and Weidinger, Stephan and Gudjonsson, Johann E. and Koks, Sulev and Kingo, Kulli and Esko, Tonu and Das, Sayantan and Metspalu, Andres and Weichenthal, Michael and Enerback, Charlotta and Krueger, Gerald G. and Voorhees, John J. and Chandran, Vinod and Rosen, Cheryl F. and Rahman, Proton and Gladman, Dafna D. and Reis, André and Nair, Rajan P. and Franke, Andre and Barker, Jonathan N. W. N. and Abecasis, Goncalo R. and Trembath, Richard C. and Elder, James T.},
doi = {10.1038/ncomms8001},
faupublication = {yes},
journal = {Nature Communications},
note = {EVALuna2:9272},
pages = {7001},
peerreviewed = {Yes},
title = {{Enhanced} meta-analysis and replication studies identify five new psoriasis susceptibility loci},
volume = {6},
year = {2015}
}
@article{faucris.246366451,
abstract = {Background: Transcription factor 4 (TCF4) has been linked to human neurodevelopmental disorders such as intellectual disability, Pitt-Hopkins Syndrome (PTHS), autism, and schizophrenia. Recent work demonstrated that TCF4 participates in the control of a wide range of neurodevelopmental processes in mammalian nervous system development including neural precursor proliferation, timing of differentiation, migration, dendritogenesis and synapse formation. TCF4 is highly expressed in the adult hippocampal dentate gyrus – one of the few brain regions where neural stem / progenitor cells generate new functional neurons throughout life. Results: We here investigated whether TCF4 haploinsufficiency, which in humans causes non-syndromic forms of intellectual disability and PTHS, affects adult hippocampal neurogenesis, a process that is essential for hippocampal plasticity in rodents and potentially in humans. Young adult Tcf4 heterozygote knockout mice showed a major reduction in the level of adult hippocampal neurogenesis, which was at least in part caused by lower stem/progenitor cell numbers and impaired maturation and survival of adult-generated neurons. Interestingly, housing in an enriched environment was sufficient to enhance maturation and survival of new neurons and to substantially augment neurogenesis levels in Tcf4 heterozygote knockout mice. Conclusion: The present findings indicate that haploinsufficiency for the intellectual disability- and PTHS-linked transcription factor TCF4 not only affects embryonic neurodevelopment but impedes neurogenesis in the hippocampus of adult mice. These findings suggest that TCF4 haploinsufficiency may have a negative impact on hippocampal function throughout adulthood by impeding hippocampal neurogenesis.},
author = {Braun, Kristina and Häberle, Benjamin and Wittmann, Marie-Theres and Lie, Dieter Chichung},
doi = {10.1186/s12868-020-00602-3},
faupublication = {yes},
journal = {BMC Neuroscience},
keywords = {Adult neurogenesis; Enriched environment; Hippocampus; Intellectual disability; PTHS; Tcf4},
note = {CRIS-Team Scopus Importer:2020-12-04},
peerreviewed = {Yes},
title = {{Enriched} environment ameliorates adult hippocampal neurogenesis deficits in {Tcf4} haploinsufficient mice},
volume = {21},
year = {2020}
}
@article{faucris.227173082,
abstract = {Background: The 15q11.2 deletion is frequently identified in the neurodevelopmental clinic. Case-control studies have associated the 15q11.2 deletion with neurodevelopmental disorders, and clinical case series have attempted to delineate a microdeletion syndrome with considerable phenotypic variability. The literature on this deletion is extensive and confusing, which is a challenge for genetic counselling. The aim of this study was to estimate the effect size of the 15q11.2 deletion and quantify its contribution to neurodevelopmental disorders. Methods: We performed meta-analyses on new and previously published case-control studies and used statistical models trained in unselected populations with cognitive assessments. We used new (n=241) and previously published (n=150) data from a clinically referred group of deletion carriers. 15q11.2 duplications (new n=179 and previously published n=35) were used as a neutral control variant. Results: The deletion decreases IQ by 4.3 points. The estimated ORs and respective frequencies in deletion carriers for intellectual disabilities, schizophrenia and epilepsy are 1.7 (3.4%), 1.5 (2%) and 3.1 (2.1%), respectively. There is no increased risk for heart malformations and autism. In the clinically referred group, the frequency and nature of symptoms in deletions are not different from those observed in carriers of the 15q11.2 duplication suggesting that most of the reported symptoms are due to ascertainment bias. Conclusions: We recommend that the deletion should be classified as € pathogenic of mild effect size'. Since it explains only a small proportion of the phenotypic variance in carriers, it is not worth discussing in the developmental clinic or in a prenatal setting.},
author = {Jønch, Aia Elise and Douard, Elise and Moreau, Clara and Van Dijck, Anke and Passeggeri, Marzia and Kooy, Frank and Puechberty, Jacques and Campbell, Carolyn and Sanlaville, Damien and Lefroy, Henrietta and Richetin, Sonia and Pain, Aurelie and Geneviève, David and Kini, Usha and Le Caignec, Cédric and Lespinasse, James and Skytte, Anne Bine and Isidor, Bertrand and Zweier, Christiane and Caberg, Jean Hubert and Delrue, Marie Ange and Møller, Rikke Steensbjerre and Bojesen, Anders and Hjalgrim, Helle and Brasch-Andersen, Charlotte and Lemyre, Emmanuelle and Ousager, Lilian Bomme and Jacquemont, Sébastien},
doi = {10.1136/jmedgenet-2018-105879},
faupublication = {yes},
journal = {Journal of Medical Genetics},
keywords = {15q11.2 copy-number variants; congenital heart disease; epilepsy; loss-of-function intolerance; neurodevelopmental disorders},
note = {CRIS-Team Scopus Importer:2019-09-27},
peerreviewed = {Yes},
title = {{Estimating} the effect size of the {15Q11}.2 {BP1}-{BP2} deletion and its contribution to neurodevelopmental symptoms: recommendations for practice},
year = {2019}
}
@article{faucris.119646824,
abstract = {Adult onset Still's disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD.We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD.We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (p c = 2.34E- 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (p c = 2.40E- 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment.Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients.},
author = {Sighart, Regina and Rech, J. and Hueber, Axel and Blank, N. and Löhr, S. and Reis, André and Sticht, Heinrich and Hüffmeier, Ulrike},
doi = {10.1007/s00296-017-3885-0},
faupublication = {yes},
journal = {Rheumatology International},
note = {EVALuna2:9382},
peerreviewed = {Yes},
title = {{Evidence} for genetic overlap between adult onset {Still}'s disease and hereditary periodic fever syndromes},
year = {2017}
}
@article{faucris.110059884,
abstract = {Glaucoma is a genetically heterogeneous disorder and is the second cause of blindness worldwide owing to the progressive degeneration of retinal ganglion neurons. Very few genes causing glaucoma were identified to this date. In this study, we screened 10 candidate genes of glaucoma between the D14S261 and D14S121 markers of chromosome 14q11, a critical region previously linked to primary open-angle glaucoma (POAG). Mutation analyses of two large cohorts of patients with POAG, normal tension glaucoma (NTG) and juvenile open-angle glaucoma (JOAG), and control subjects, found only association of non-synonymous heterozygous variants of the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) with POAG, NTG and JOAG. The 20 non-synonymous variants identified in RPGRIP1 were all distinct from variants causing photoreceptor dystrophies and were found throughout all but one domain (RPGR-interacting domain) of RPGRIP1. Among them, 14 missense variants clustered within or around the C2 domains of RPGRIP1. Yeast two-hybrid analyses of a subset of the missense mutations within the C2 domains of RPGRIP1 shows that five of them (p.R598Q, p.A635G, p.T806I, p.A837G and p.I838V) decrease the association of the C2 domains with nephrocystin-4 (NPHPH). When considering only these five confirmed C2-domain mutations, the association remains statistically significant (P=0.001). Altogether, the data support that heterozygous non-synonymous variants of RPGRIP1 may cause or increase the susceptibility to various forms of glaucoma and that among other factors, physical impairment of the interaction of RPGRIP1with different proteins may contribute to the pathogenesis of forms of glaucoma.},
author = {Fernández Martinez, Lorena and Letteboer, Stef and Mardin, Christian Y. and Weisschuh, Nicole and Gramer, Eugen and Weber, Bernhard H. F. and Rautenstrauß, Bernd and Ferreira, Paulo A. and Kruse, Friedrich and Reis, André and Roepman, Ronald and Pasutto, Francesca},
doi = {10.1038/ejhg.2010.217},
faupublication = {yes},
journal = {European journal of human genetics},
note = {EVALuna2:9085},
pages = {445-51},
peerreviewed = {Yes},
title = {{Evidence} for {RPGRIP1} gene as risk factor for primary open angle glaucoma},
volume = {19},
year = {2011}
}
@article{faucris.218412578,
abstract = {Height is a heritable and highly heterogeneous trait. Short stature affects 3% of the population and in most cases is genetic in origin. After excluding known causes, 67% of affected individuals remain without diagnosis. To identify novel candidate genes for short stature, we performed exome sequencing in 254 unrelated families with short stature of unknown cause and identified variants in 63 candidate genes in 92 (36%) independent families. Based on systematic characterization of variants and functional analysis including expression in chondrocytes, we classified 13 genes as strong candidates. Whereas variants in at least two families were detected for all 13 candidates, two genes had variants in 6 (UBR4) and 8 (LAMA5) families, respectively. To facilitate their characterization, we established a clustered network of 1025 known growth and short stature genes, which yielded 29 significantly enriched clusters, including skeletal system development, appendage development, metabolic processes, and ciliopathy. Eleven of the candidate genes mapped to 21 of these clusters, including CPZ, EDEM3, FBRS, IFT81, KCND1, PLXNA3, RASA3, SLC7A8, UBR4, USP45, and ZFHX3. Fifty additional growth-related candidates we identified await confirmation in other affected families. Our study identifies Mendelian forms of growth retardation as an important component of idiopathic short stature.},
author = {Hauer, Nadine and Popp, Bernt and Taher, Leila and Vogl, Carina and Dhandapany, Perundurai S. and Büttner, Christian and Uebe, Steffen and Sticht, Heinrich and Ferrazzi, Fulvia and Ekici, Arif Bülent and De Luca, Alessandro and Klinger, Patricia and Kraus, Cornelia and Zweier, Christiane and Wiesener, Antje and Jamra, Rami Abou and Kunstmann, Erdmute and Rauch, Anita and Wieczorek, Dagmar and Jung, Anna Marie and Rohrer, Tilman R. and Zenker, Martin and Dörr, Helmuth-Günther and Reis, André and Thiel, Christian},
doi = {10.1038/s41431-019-0362-0},
faupublication = {yes},
journal = {European journal of human genetics},
note = {CRIS-Team Scopus Importer:2019-05-24},
peerreviewed = {Yes},
title = {{Evolutionary} conserved networks of human height identify multiple {Mendelian} causes of short stature},
year = {2019}
}
@article{faucris.119649024,
abstract = {High throughput sequencing has greatly advanced disease gene identification, especially in heterogeneous entities. Despite falling costs this is still an expensive and laborious technique, particularly when studying large cohorts. To address this problem we applied Exome Pool-Seq as an economic and fast screening technology in neurodevelopmental disorders (NDDs). Sequencing of 96 individuals can be performed in eight pools of 12 samples on less than one Illumina sequencer lane. In a pilot study with 96 cases we identified 27 variants, likely or possibly affecting function. Twenty five of these were identified in 923 established NDD genes (based on SysID database, status November 2016) (ACTB, AHDC1, ANKRD11, ATP6V1B2, ATRX, CASK, CHD8, GNAS, IFIH1, KCNQ2, KMT2A, KRAS, MAOA, MED12, MED13L, RIT1, SETD5, SIN3A, TCF4, TRAPPC11, TUBA1A, WAC, ZBTB18, ZMYND11), two in 543 (SysID) candidate genes (ZNF292, BPTF), and additionally a de novo loss-of-function variant in LRRC7, not previously implicated in NDDs. Most of them were confirmed to be de novo, but we also identified X-linked or autosomal-dominantly or autosomal-recessively inherited variants. With a detection rate of 28%, Exome Pool-Seq achieves comparable results to individual exome analyses but reduces costs by >85%. Compared with other large scale approaches using Molecular Inversion Probes (MIP) or gene panels, it allows flexible re-analysis of data. Exome Pool-Seq is thus well suited for large-scale, cost-efficient and flexible screening in characterized but heterogeneous entities like NDDs.},
author = {Popp, Bernt and Ekici, Arif Bülent and Thiel, Christian and Hoyer, Juliane and Wiesener, Antje and Kraus, Cornelia and Reis, André and Zweier, Christiane},
doi = {10.1038/s41431-017-0022-1},
faupublication = {yes},
journal = {European journal of human genetics},
note = {EVALuna2:9387},
peerreviewed = {Yes},
title = {{Exome} {Pool}-{Seq} in neurodevelopmental disorders},
year = {2017}
}
@inproceedings{faucris.248108435,
address = {LONDON},
author = {Popp, B. and Vasileiou, G. and Zweier, M. and Ekici, Arif Bülent and Moortgat, S. and Lederer, D. and Maystadt, I. and Destree, A. and Drunat, S. and Verloes, A. and Rauch, A. and Steindl, K. and Van Maldergem, L. and Piard, J. and Brischoux, E. B. and Engel, C. and Serey-Gaut, M. and Reis, André and Zweier, Christiane},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {332-333},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Exome} {Pool}-{Seq} {Reloaded}},
year = {2020}
}
@article{faucris.119648364,
abstract = {Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 × 10-8, OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency < 0.01) via gene-wide aggregation testing (IFIH1: pburden = 2.53 × 10-7, OR = 0.707; TYK2: pburden = 6.17 × 10-4, OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.},
author = {Dand, Nick and Mucha, Soeren and Tsoi, Lam C. and Mahil, Satveer K. and Stuart, Philip E. and Arnold, Andreas and Baurecht, Hansjoerg and Burden, A. David and Duffin, Kristina Callis and Chandran, Vinod and Curtis, Charles J. and Das, Sayantan and Ellinghaus, David and Ellinghaus, Eva and Enerback, Charlotta and Esko, Tonu and Gladman, Dafna D. and Griffiths, Christopher E. M. and Gudjonsson, Johann E. and Hoffman, Per and Homuth, Georg and Hueffmeier, Ulrike and Krueger, Gerald G. and Laudes, Matthias and Lee, Sang Hyuck and Lieb, Wolfgang and Lim, Henry W. and Loehr, Sabine and Mrowietz, Ulrich and Mueller-Nurayid, Martina and Noethen, Markus and Peters, Annette and Rahman, Proton and Reis, André and Reynolds, Nick J. and Rodriguez, Elke and Schmidt, Carsten O. and Spain, Sarah L. and Strauch, Konstantin and Tejasvi, Trilokraj and Voorhees, John J. and Warren, Richard B. and Weichenthal, Michael and Weidinger, Stephan and Zawistowski, Matthew and Nair, Rajan P. and Capon, Francesca and Smith, Catherine H. and Trembath, Richard C. and Abecasis, Goncalo R. and Elder, James T. and Franke, Andre and Simpson, Michael A. and Barker, Jonathan N.},
doi = {10.1093/hmg/ddx328},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:9384},
pages = {4301-4313},
peerreviewed = {Yes},
title = {{Exome}-wide association study reveals novel psoriasis susceptibility locus at {TNFSF15} and rare protective alleles in genes contributing to type {I} {IFN} signalling},
volume = {26},
year = {2017}
}
@inproceedings{faucris.248111651,
address = {LONDON},
author = {Begemann, A. and Sticht, Heinrich and Mcwalter, K. and Vitobello, A. and Faivre, L. and Alhaddad, B. and Banka, S. and Becker, J. and Bierhals, T. and Brown, K. and Bruel, A. and Brunet, T. and Carneiro, M. and Cremer, K. and Day, R. and Denomme-Pichon, A. and Dyment, D. A. and Engels, H. and Fisher, R. and Glassford, M. and Goh, E. S. and Hajianpour, M. and Haertel, L. R. M. and Hauer, Nadine and Hempel, M. and Herget, T. and Kraus, Cornelia and Le Guyader, G. and Lesca, G. and Mau-Them, F. T. and Mcdermott, J. H. and Meyer, P. and Ounap, K. and Popp, Bernt and Reimand, T. and Riedhammer, K. M. and Russo, M. and Sadleir, L. and Schuler, E. and Siegel, G. and Syrbe, S. and Van Der Ven, A. T. and Verloes, A. and Willems, M. and Zweier, Christiane and Steindl, K. and Zweier, M. and Rauch, A.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {329-331},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Expanding} the clinical and molecular spectrum of the novel {CYFIP2}-related neurodevelopmental disorder and functional proof of aberrant {WRC}-mediated actin dynamics},
year = {2020}
}
@article{faucris.107199004,
abstract = {Biallelic mutations of UBE3B have recently been shown to cause Kaufman oculocerebrofacial syndrome (also reported as blepharophimosis-ptosis-intellectual disability syndrome), an autosomal recessive condition characterized by hypotonia, developmental delay, intellectual disability, congenital anomalies, characteristic facial dysmorphic features, and low cholesterol levels. To date, six patients with either missense mutations affecting the UBE3B HECT domain or truncating mutations have been described. Here, we report on the identification of homozygous or compound heterozygous UBE3B mutations in six additional patients from five unrelated families using either targeted UBE3B sequencing in individuals with suggestive facial dysmorphic features, or exome sequencing. Our results expand the clinical and mutational spectrum of the UBE3B-related disorder in several ways. First, we have identified UBE3B mutations in individuals who previously received distinct clinical diagnoses: two sibs with Toriello-Carey syndrome as well as the patient reported to have a "new" syndrome by Buntinx and Majewski in 1990. Second, we describe the adult phenotype and clinical variability of the syndrome. Third, we report on the first instance of homozygous missense alterations outside the HECT domain of UBE3B, observed in a patient with mildly dysmorphic facial features. We conclude that UBE3B mutations cause a clinically recognizable and possibly underdiagnosed syndrome characterized by distinct craniofacial features, hypotonia, failure to thrive, eye abnormalities, other congenital malformations, low cholesterol levels, and severe intellectual disability. We review the UBE3B-associated phenotypes, including forms that can mimick Toriello-Carey syndrome, and suggest the single designation "Kaufman oculocerebrofacial syndrome".},
author = {Basel-Vanagaite, Lina and Yilmaz, Rustem and Tang, Sha and Reuter, Miriam and Rahner, Nils and Grange, Dorothy K. and Mortenson, Megan and Koty, Patrick and Feenstra, Heather and Gonzalez, Kelly D. Farwell and Sticht, Heinrich and Boddaert, Nathalie and Desir, Julie and Anyane-Yeboa, Kwame and Zweier, Christiane and Reis, André and Kubisch, Christian and Jewett, Tamison and Zeng, Wenqi and Borck, Guntram},
doi = {10.1007/s00439-014-1436-2},
faupublication = {yes},
journal = {Human genetics},
note = {EVALuna2:9227},
pages = {939-49},
peerreviewed = {Yes},
title = {{Expanding} the clinical and mutational spectrum of {Kaufman} oculocerebrofacial syndrome with biallelic {UBE3B} mutations},
volume = {133},
year = {2014}
}
@article{faucris.123876544,
abstract = {Primary congenital glaucoma (PCG) and early onset glaucomas are one of the major causes of children and young adult blindness worldwide. Both autosomal recessive and dominant inheritance have been described with involvement of several genes including CYP1B1, FOXC1, PITX2, MYOC and PAX6. However, mutations in these genes explain only a small fraction of cases suggesting the presence of further candidate genes.To elucidate further genetic causes of these conditions whole exome sequencing (WES) was performed in an Italian patient, diagnosed with PCG and retinal detachment, and his unaffected parents. Sanger sequencing of the complete coding region of COL1A1 was performed in a total of 26 further patients diagnosed with PCG or early onset glaucoma. Exclusion of pathogenic variations in known glaucoma genes as CYP1B1, MYOC, FOXC1, PITX2 and PAX6 was additionally done per Sanger sequencing and Multiple Ligation-dependent Probe Amplification (MLPA) analysis.In the patient diagnosed with PCG and retinal detachment, analysis of WES data identified compound heterozygous variants in COL1A1 (p.Met264Leu; p.Ala1083Thr). Targeted COL1A1 screening of 26 additional patients detected three further heterozygous variants (p.Arg253*, p.Gly767Ser and p.Gly154Val) in three distinct subjects: two of them diagnosed with early onset glaucoma and mild form of osteogenesis imperfecta (OI), one patient with a diagnosis of PCG at age 4 years. All five variants affected evolutionary, highly conserved amino acids indicating important functional restrictions. Molecular modeling predicted that the heterozygous variants are dominant in effect and affect protein stability and thus the amount of available protein, while the compound heterozygous variants act as recessive alleles and impair binding affinity to two main COL1A1 binding proteins: Hsp47 and fibronectin.Dominant inherited mutations in COL1A1 are known causes of connective tissues disorders such as OI. These disorders are also associated with different ocular abnormalities, although recognition of the common pathology for both features is seldom being recognized. Our results expand the role of COL1A1 mutations in different forms of early-onset glaucoma with and without signs of OI. Thus, we suggest including COL1A1 mutation screening in the genetic work-up of glaucoma cases and detailed ophthalmic examinations with fundus analysis in patients with OI.},
author = {Mauri, Lucia and Uebe, Steffen and Sticht, Heinrich and Vossmerbaeumer, Urs and Weisschuh, Nicole and Manfredini, Emanuela and Maselli, Edoardo and Patrosso, Mariacristina and Weinreb, Robert N. and Penco, Silvana and Reis, André and Pasutto, Francesca},
doi = {10.1186/s13023-016-0495-y},
faupublication = {yes},
journal = {Orphanet Journal of Rare Diseases},
note = {EVALuna2:9324},
pages = {108},
peerreviewed = {Yes},
title = {{Expanding} the clinical spectrum of {COL1A1} mutations in different forms of glaucoma},
volume = {11},
year = {2016}
}
@article{faucris.123087404,
abstract = {N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ line mosaicism in another girl and her more severely affected and deceased brother. In vitro enzymatic assays for the novel, recurrent mutations p.(Arg83Cys) and p.(Phe128Leu) revealed reduced catalytic activity. X-inactivation was random in five females. The core phenotype of X-linked NAA10-related N-terminal-acetyltransferase deficiency in both males and females includes developmental delay, severe intellectual disability, postnatal growth failure with severe microcephaly, and skeletal or cardiac anomalies. Genotype-phenotype correlations within and between both genders are complex and may include various factors such as location and nature of mutations, enzymatic stability and activity, and X-inactivation in females.},
author = {Saunier, Chloe and Stove, Svein Isungset and Popp, Bernt and Gerard, Benedicte and Blenski, Marina and Ahmew, Nicholas and De Bie, Charlotte and Goldenberg, Paula and Isidor, Bertrand and Keren, Boris and Leheup, Bruno and Lampert, Laetitia and Mignot, Cyril and Tezcan, Kamer and Mancini, Grazia M. S. and Nava, Caroline and Wasserstein, Melissa and Bruel, Ange-Line and Thevenon, Julien and Masurel, Alice and Duffourd, Yannis and Kuentz, Paul and Huet, Frederic and Riviere, Jean-Baptiste and Van Slegtenhorst, Marjon and Faivre, Laurence and Piton, Amelie and Reis, André and Arnesen, Thomas and Thauvin-Robinet, Christel and Zweier, Christiane},
doi = {10.1002/humu.23001},
faupublication = {yes},
journal = {Human Mutation},
note = {EVALuna2:9314},
pages = {755-64},
peerreviewed = {Yes},
title = {{Expanding} the {Phenotype} {Associated} with {NAA10}-{Related} {N}-{Terminal} {Acetylation} {Deficiency}},
volume = {37},
year = {2016}
}
@article{faucris.289675268,
abstract = {We report on a female individual with feeding difficulties, constipation, poor overall growth, periventricular lesions resembling gliosis in brain MRI, recurrent otitis media with palsy of facial nerve, distinct facial features, and pronounced delay in speech development. The latter was the most prominent feature. Molecular karyotyping revealed a heterozygous de novo deletion of 4.353 Mb at chromosome 12q21.33q22. This report expands the number of described individuals with heterozygous deletions at 12q21.33, their clinical spectrum and highlights the clinical variability, even in individuals with deletion of the same genes. Furthermore, our findings indicate a role of BTG1 (OMIM *109580) in speech development.},
author = {Blum, Katalin and Krumbiegel, Mandy and Kraus, Cornelia and Reis, André and Hüffmeier, Ulrike},
doi = {10.1016/j.ejmg.2023.104717},
faupublication = {yes},
journal = {European Journal of Medical Genetics},
keywords = {12q21.33; Microdeletion; Speech developmental delay},
note = {CRIS-Team Scopus Importer:2023-02-24},
peerreviewed = {Yes},
title = {{Expanding} the phenotype of 12q21 deletions: {A} role of {BTG1} in speech development?},
volume = {66},
year = {2023}
}
@inproceedings{faucris.248111155,
address = {LONDON},
author = {Ruaud, L. and Drunat, S. and Ernault, A. and Capri, Y. and Van Maldergem, L. and Engel, C. and Altuzarra, C. and Bayat, A. and Moortgart, S. and Maystadt, I. and Abramowicz, M. and Zweier, Christiane and Lorenz, I. and Haye, D. and Giuliano, F. and Vaessen, S. and Servais, L. and Di Maria, E. and Faravelli, F. and Kohlhase, J. and Bast, T. and Miladi, N. and Agadr, A. and Auvin, S. and Verloes, A. and Passemard, S.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {421-422},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Expanding} the spectrum of {WDR62} mutations : description of new cases},
year = {2020}
}
@inproceedings{faucris.228294139,
address = {LONDON},
author = {Hauer, Nadine and Vogl, C. and Popp, Bernt and Buettner, C. and Uebe, S. and Sticht, Heinrich and Ekici, Arif Bülent and Klinger, Patricia and Kraus, Cornelia and Krumbiegel, M. and Wiesener, A. and Dörr, Helmuth-Günther and Wiesmann da Silva Reis, André and Thiel, Christian},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2019-06-15/2019-06-18},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {1380-1380},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{Exploring} the phenotypical spectrum of {BRD4} defects},
venue = {Gothenburg, SWEDEN},
year = {2019}
}
@article{faucris.310124452,
abstract = {Background: Individual radiosensitivity is an important factor in the occurrence of undesirable consequences of radiotherapy. The potential for increased radiosensitivity has been linked to highly penetrant heterozygous mutations in DNA repair genes such as BRCA1 and BRCA2. By studying the chromosomal radiosensitivity of BRCA1/2 mutation carriers compared to the general population, we study whether increased chromosomal radiation sensitivity is observed in patients with BRCA1/2 variants. Methods: Three-color-fluorescence in situ hybridization was performed on ex vivo-irradiated peripheral blood lymphocytes from 64 female patients with a heterozygous germline BRCA1 or BRCA2 mutation. Aberrations in chromosomes #1, #2 and #4 were analyzed. Mean breaks per metaphase (B/M) served as the parameter for chromosomal radiosensitivity. The results were compared with chromosomal radiosensitivity in a cohort of generally healthy individuals and patients with rectal cancer or breast cancer. Results: Patients with BRCA1/2 mutations (n = 64; B/M 0.47) overall showed a significantly higher chromosomal radiosensitivity than general healthy individuals (n = 211; B/M 0.41) and patients with rectal cancer (n = 379; B/M 0.44) and breast cancer (n = 147; B/M 0.45) without proven germline mutations. Chromosomal radiosensitivity varied depending on the locus of the BRCA1/2 mutation. Conclusions: BRCA1/2 mutations result in slightly increased chromosomal sensitivity to radiation. A few individual patients have a marked increase in radiation sensitivity. Therefore, these patients are at a higher risk for adverse therapeutic consequences.},
author = {Zuhair Kassem, Tara and Wunderle, Marius and Kuhlmann, Lukas and Rübner, Matthias and Hübner, Hanna and Hoyer, Juliane and Reis, André and Fasching, Peter and Beckmann, Matthias and Hack, Carolin and Fietkau, Rainer and Distel, Luitpold},
doi = {10.3390/cimb45080418},
faupublication = {yes},
journal = {Current Issues in Molecular Biology},
keywords = {BRCA1; BRCA2; breast cancer; chromosomal radiosensitivity; FISH assay; radiation oncology; radiation sensitivity testing; radiotherapy},
note = {CRIS-Team Scopus Importer:2023-09-08},
pages = {6618-6633},
peerreviewed = {Yes},
title = {{Ex} {Vivo} {Chromosomal} {Radiosensitivity} {Testing} in {Patients} with {Pathological} {Germline} {Variants} in {Breast} {Cancer} {High}-{Susceptibility} {Genes} {BReast} {CAncer} 1 and {BReast} {CAncer} 2},
volume = {45},
year = {2023}
}
@article{faucris.279556062,
abstract = {Aortic dissection is a life-threatening cardiovascular disease. Hereditary disorders are responsible for a small percentage of cases. Nonetheless, it is important to identify genetic causes, as they are often autosomal dominantly inherited and are of life-saving importance if we can identify persons at risk. Mutations of the ACTA2 gene are the most common cause of non-syndromic familial aortic disease. Exploration of the genetic background in suspected familial cases and determination of the exact etiology are mandatory for management and establishing appropriate follow-up strategies due to the risk of fatal recurrences. Herein, we present a 21-year-old male with a familial acute aortic dissection associated with novel ACTA2 germline variant and discuss the management and surveillance considerations.},
author = {Strecker, Thomas and Wiesmueller, Felix and Rudnik-Schoeneborn, Sabine and Hoyer, Juliane and Wiesmann da Silva Reis, André and Weyand, Michael and Agaimy, Abbas},
doi = {10.1007/s00428-022-03366-9},
faupublication = {yes},
journal = {Virchows Archiv},
note = {CRIS-Team WoS Importer:2022-08-05},
peerreviewed = {Yes},
title = {{Familial} acute aortic dissection associated with a novel {ACTA2} germline variant},
year = {2022}
}
@article{faucris.307362712,
abstract = {Objective: Identification of clinically relevant determinants for acute coronary syndromes (ACS) promises reduction of ACS-associated mortality. C-reactive protein (CRP) has proved to be useful identifying people at risk for cardiovascular events. However, it is unknown whether genetic variants at Fcγ receptor IIa (FcγRIIa), the main receptor for CRP, are involved in CRP-related cardiovascular risk. We evaluated the potential impact of FcγRIIa through a genetic association study in patients with ACS. Methods and results: We conducted a genetic association study among 701 consecutive patients with first event of ACS compared to 467 patients with stable angina pectoris. All patients were genotyped for a frequent functional variant at position 131 of the mature FcγRIIa, where the arginine (R) allele results in an increased signal transduction upon CRP binding. In our study, the R/R131 genotype was significantly associated with ACS as the first manifestation of coronary artery disease (P = 1.2 × 10-9, odds ratio 2.86, 95% CI: 2.06-3.99) compared to the non-R/R131 genotype. Conclusions: Our data show a genetic association of the FcγRIIa R/R131 genotype with a more frequent occurrence of ACS as the first manifestation of coronary artery disease, probably mediated via its interaction with CRP. Genotyping of this FcγRIIa variant could help to improve risk stratification in the course of coronary disease in the future. © 2009 Elsevier Ireland Ltd. All rights reserved.},
author = {Raaz, Dorette and Herrmann, Martin and Ekici, Arif Bülent and Klinghammer, Lutz and Lausen, Berthold and Voll, Reinhard E. and Leusen, Jeanette H.W. and van de Winkel, Jan G.J. and Daniel, Werner and Reis, André and Garlichs, Christoph},
doi = {10.1016/j.atherosclerosis.2009.01.013},
faupublication = {yes},
journal = {Atherosclerosis},
keywords = {Acute coronary syndrome; Fcγ receptor IIa; Gene polymorphism; Inflammation},
note = {CRIS-Team Scopus Importer:2023-07-10},
pages = {512-516},
peerreviewed = {Yes},
title = {{FcγRIIa} genotype is associated with acute coronary syndromes as first manifestation of coronary artery disease},
volume = {205},
year = {2009}
}
@article{faucris.109626704,
abstract = {Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.},
author = {Painter, Jodie N. and O'Mara, Tracy A. and Batra, Jyotsna and Cheng, Timothy and Lose, Felicity A. and Dennis, Joe and Michailidou, Kyriaki and Tyrer, Jonathan P. and Ahmed, Shahana and Ferguson, Kaltin and Healey, Catherine S. and Kaufmann, Susanne and Hillman, Kristine M. and Walpole, Carina and Moya, Leire and Pollock, Pamela and Jones, Angela and Howarth, Kimberley and Martin, Lynn and Gorman, Maggie and Hodgson, Shirley and Magdalena Echeverry De Polanco, Ma. and Sans, Monica and Carracedo, Angel and Castellvi-Bel, Sergi and Rojas-Martinez, Augusto and Santos, Erika and Teixeira, Manuel R. and Carvajal-Carmona, Luis and Shu, Xiao-Ou and Long, Jirong and Zheng, Wei and Xiang, Yong-Bing and Montgomery, Grant W. and Webb, Penelope M. and Scott, Rodney J. and Mcevoy, Mark and Attia, John and Holliday, Elizabeth and Martin, Nicholas G. and Nyholt, Dale R. and Henders, Anjali K. and Fasching, Peter A. and Hein, Alexander and Beckmann, Matthias and Renner, Stefan and Doerk, Thilo and Hillemanns, Peter and Duerst, Matthias and Runnebaum, Ingo and Lambrechts, Diether and Coenegrachts, Lieve and Schrauwen, Stefanie and Amant, Frederic and Winterhoff, Boris and Dowdy, Sean C. and Goode, Ellen L. and Teoman, Attila and Salvesen, Helga B. and Trovik, Jone and Njolstad, Tormund S. and Werner, Henrica M. J. and Ashton, Katie and Proietto, Tony and Otton, Geoffrey and Tzortzatos, Gerasimos and Mints, Miriam and Tham, Emma and Hall, Per and Czene, Kamila and Liu, Jianjun and Li, Jingmei and Hopper, John L. and Southey, Melissa C. and Ekici, Arif Bülent and Rübner, Matthias and Johnson, Nicola and Peto, Julian and Burwinkel, Barbara and Marme, Frederik and Brenner, Hermann and Dieffenbach, Aida K. and Meindl, Alfons and Brauch, Hiltrud and Lindblom, Annika and Depreeuw, Jeroen and Moisse, Matthieu and Chang-Claude, Jenny and Rudolph, Anja and Couch, Fergus J. and Olson, Janet E. and Giles, Graham G. and Bruinsma, Fiona and Cunningham, Julie M. and Fridley, Brooke L. and Borresen-Dale, Anne-Lise and Kristensen, Vessela N. and Cox, Angela and Swerdlow, Anthony J. and Orr, Nicholas and Bolla, Manjeet K. and Wang, Qin and Weber, Rachel Palmieri and Chen, Zhihua and Shah, Mitul and French, Juliet D. and Pharoah, Paul D. P. and Dunning, Alison M. and Tomlinson, Ian and Easton, Douglas F. and Edwards, Stacey L. and Thompson, Deborah J. and Spurdle, Amanda B.},
doi = {10.1093/hmg/ddu552},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:9243},
pages = {1478-92},
peerreviewed = {Yes},
title = {{Fine}-mapping of the {HNF1B} multicancer locus identifies candidate variants that mediate endometrial cancer risk},
volume = {24},
year = {2015}
}
@article{faucris.274496015,
abstract = {The accumulation of alpha-synuclein in Lewy bodies and Lewy neurites of different neuronal populations is one of the neuropathological hallmarks in Parkinson disease (PD). Overexpression of human wildtype or mutant alpha-synuclein affects the generation of new neurons in the adult dentate gyrus (DG) of the hippocampus in models of PD. Hippocampal dysfunction with reduced neurogenesis plays an important role in the pathogenesis of depression, an important non-motor symptom in PD. Moreover, effective antidepressant treatment is still an unmet need in PD. The present study explored if impaired hippocampal neurogenesis in the A53T transgenic animal model of PD may be restored by chronic oral application of the selective serotonin reuptake inhibitor (SSRI) fluoxetine. First, we determined the expression pattern of transgenic mutant A53T synuclein in developing DG neurons and showed early expression of the transgene linked to a severely impaired neurogenesis. After chronic fluoxetine treatment we observed an increased adult neurogenesis in the hippocampus of more than threefold in treated A53T mice compared with controls. The pro-neurogenic effect of chronic fluoxetine application is predominantly related to an increased proliferation of neural precursor cells in the DG, and to a lesser extent by induction of differentiation into mature neurons. Analysis of the underlying mechanisms revealed an induction of brain-derived and glial cell-derived neurotrophic factor levels as a result of fluoxetine treatment. This study underlines the large potential of SSRI-dependent mechanisms to stimulate adult hippocampal neurogenesis in alpha-synuclein models and may lead to novel means to improve neuropsychiatric symptoms in PD.},
author = {Kohl, Zacharias and Winner, Beate and Ubhi, Kiren and Rockenstein, Edward and Mante, Michael and Muench, Martina and Barlow, Carolee and Carter, Todd and Masliah, Eliezer and Winkler, Jürgen},
doi = {10.1111/j.1460-9568.2011.07933.x},
faupublication = {yes},
journal = {European Journal of Neuroscience},
note = {EVALuna2:25298},
pages = {10-9},
peerreviewed = {Yes},
title = {{Fluoxetine} rescues impaired hippocampal neurogenesis in a transgenic {A53T} synuclein mouse model.},
volume = {35},
year = {2012}
}
@article{faucris.208857013,
abstract = {Autophagy is a conserved catabolic pathway with emerging functions in mammalian neurodevelopment and human neurodevelopmental diseases. The mechanisms controlling autophagy in neuronal development are not fully understood. Here, we found that conditional deletion of the Forkhead Box O transcription factors FoxO1, FoxO3, and FoxO4 strongly impaired autophagic flux in developing neurons of the adult mouse hippocampus. Moreover, FoxO deficiency led to altered dendritic morphology, increased spine density, and aberrant spine positioning in adult-generated neurons. Strikingly, pharmacological induction of autophagy was sufficient to correct abnormal dendrite and spine development of FoxO-deficient neurons. Collectively, these findings reveal a novel link between FoxO transcription factors, autophagic flux, and maturation of developing neurons.
},
author = {Schäffner, Iris and Minakaki, Georgia and Khan, M. Amir and Balta, Elli-Anna and Schlötzer-Schrehardt, Ursula and Schwarz, Tobias J. and Beckervordersandforth, Ruth and Winner, Beate and Webb, Ashley E. and Depinho, Ronald A. and Paik, Jihye and Wurst, Wolfgang and Klucken, Jochen and Lie, Dieter Chichung},
doi = {10.1016/j.neuron.2018.08.017},
faupublication = {yes},
journal = {Neuron},
note = {EVALuna2:34732},
pages = {1188-1203.e6},
peerreviewed = {Yes},
title = {{FoxO} {Function} {Is} {Essential} for {Maintenance} of {Autophagic} {Flux} and {Neuronal} {Morphogenesis} in {Adult} {Neurogenesis}},
volume = {99},
year = {2018}
}
@article{faucris.122001044,
abstract = {Disruptions of the FOXP2 gene, encoding a forkhead transcription factor, are the first known monogenic cause of a speech and language disorder. So far, mainly chromosomal rearrangements such as translocations or larger deletions affecting FOXP2 have been reported. Intragenic deletions or convincingly pathogenic point mutations in FOXP2 have up to date only been reported in three families. We thus aimed at a further characterisation of the mutational and clinical spectrum.Chromosomal microarray testing, trio exome sequencing, multigene panel sequencing and targeted sequencing of FOXP2 were performed in individuals with variable developmental disorders, and speech and language deficits.We identified four different truncating mutations, two novel missense mutations within the forkhead domain and an intragenic deletion in FOXP2 in 14 individuals from eight unrelated families. Mutations occurred de novo in four families and were inherited from an affected parent in the other four. All index patients presented with various manifestations of language and speech impairment. Apart from two individuals with normal onset of speech, age of first words was between 4 and 7 years. Articulation difficulties such as slurred speech, dyspraxia, stuttering and poor pronunciation were frequently noted. Motor development was normal or only mildly delayed. Mild cognitive impairment was reported for most individuals.By identifying intragenic deletions or mutations in 14 individuals from eight unrelated families with variable developmental delay/cognitive impairment and speech and language deficits, we considerably broaden the mutational and clinical spectrum associated with aberrations in FOXP2.},
author = {Reuter, Miriam and Riess, Angelika and Moog, Ute and Briggs, Tracy A. and Chandler, Kate E. and Rauch, Anita and Stampfer, Miriam and Steindl, Katharina and Glaeser, Dieter and Joset, Pascal and Krumbiegel, Mandy and Rabe, Harald and Schulte-Mattler, Uta and Bauer, Peter and Beck-Woedl, Stefanie and Kohlhase, Juergen and Reis, André and Zweier, Christiane},
doi = {10.1136/jmedgenet-2016-104094},
faupublication = {yes},
journal = {Journal of Medical Genetics},
note = {EVALuna2:9348},
pages = {64-72},
peerreviewed = {Yes},
title = {{FOXP2} variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum},
volume = {54},
year = {2017}
}
@article{faucris.124090384,
abstract = {The role of AP-1 transcription factors in early B cell development and function is still incompletely characterized. Here we address the role of Fra-2 in B cell differentiation. Deletion of Fra-2 leads to impaired B cell proliferation in the bone marrow. In addition, IL-7-stimulated pro-B cell cultures revealed a reduced differentiation from large pre-B cells to small B cells and immature B cells. Gene profiling and chromatin immunoprecipitation sequencing analyses unraveled a transcriptional reduction of the transcription factors Foxo1, Irf4, Ikaros, and Aiolos in Fra-2-deficient B cells. Moreover, expression of IL7R? and Rag 1/2, downstream targets of Irf4 and Foxo1, were also reduced in the absence of Fra-2. Pro-B cell proliferation and small pre-B cell differentiation were fully rescued by expression of Foxo1 and Irf4 in Fra-2-deficient pro-B cells. Hence, Fra-2 is a key upstream regulator of Foxo1 and Irf4 expression and influences proliferation and differentiation of B cells at multiple stages.},
author = {Ubieta, Kenia and Garcia, Mireia and Groetsch, Bettina and Uebe, Steffen and Stein, Merle and Ekici, Arif Bülent and Schett, Georg and Mielenz, Dirk and Bozec, Aline and Weber, Georg},
doi = {10.1084/jem.20160514},
faupublication = {yes},
journal = {Journal of Experimental Medicine},
note = {EVALuna2:9366},
peerreviewed = {Yes},
title = {{Fra}-2 regulates {B} cell development by enhancing {IRF4} and {Foxo1} transcription},
year = {2017}
}
@inproceedings{faucris.228302768,
address = {LONDON},
author = {Balci, T. B. and Wang, L. and Lalani, S. and Heide, S. and Keren, B. and Mignot, C. and Morley, G. and Walia, J. and Wheeler, P. and Lemons, J. and Buritica, D. Rodriguez and Riberi, E. and Biamino, E. and Schatz, K. and Gunay-Aygun, M. and Wiesener, A. and Zweier, Christiane and Wentzensen, I. and Siu, V. M. and Bi, W.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2019-06-15/2019-06-18},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {1494-1495},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{Fruits} of {Genomic} {Match}-making: {De} {Novo} {Variants} in {PRR12} are {Associated} with a {Spectrum} of {Eye} and {Neurodevelopmental} {Anomalies}},
venue = {Gothenburg, SWEDEN},
year = {2019}
}
@article{faucris.108555964,
abstract = {Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR serves as a cAMP-stimulated chloride channel in a wide range of epithelial tissues and its dysfunction is a hallmark of CF. Over 1400 mutations in the CFTR gene are known, but functional data exist only for a minority of the mutant channels. The aim of the present study was to functionally characterize a novel CFTR mutation identified in a patient with atypical CF. Full length sequencing of the patient's CFTR gene revealed a homozygous C to T transition at nucleotide position 331 (CCT>TCT), which results in a P67S amino acid substitution. Mutant and wild-type CFTR were heterologously expressed in Xenopus laevis oocytes. CFTR whole-cell currents were studied using the two-electrode voltage-clamp technique. Channel surface expression was assessed by a chemiluminescence assay. Expression of P67S-CFTR resulted in functional CFTR chloride channels. However, the CFTR chloride conductance observed in oocytes expressing the mutant channel averaged only 24% of that in oocytes expressing wild-type CFTR. Similarly, surface expression of the mutant channel was reduced. In contrast, the mutation did not alter the anion selectivity of the channel, and Western blot analysis indicated a similar protein expression level of mutant and wild-type CFTR. Our findings indicate that the P67S mutation reduces CFTR chloride channel function by reducing channel surface expression. The mild disease phenotype of the patient indicates that the residual function of the mutant channel is sufficient to prevent the development of severe CF symptoms. Copyright © 2007 S. Karger AG.},
author = {Kraus, Cornelia and Reis, André and Naehrlich, Lutz and Dötsch, Jörg and Korbmacher, Christoph and Rauh, Robert},
doi = {10.1159/000102387},
faupublication = {yes},
journal = {Cellular Physiology and Biochemistry},
keywords = {CFTR; Chloride channel; Cystic fibrosis; Electrophysiology; P67S mutation; Pancreatic insufficiency; Surface expression; Xenopus laevis oocytes},
note = {UnivIS-Import:2015-04-14:Pub.2007.med.IPK.LPVP.functi},
pages = {239-248},
peerreviewed = {Yes},
title = {{Functional} characterization of a novel {CFTR} mutation {P67S} identified in a patient with atypical cystic fibrosis},
year = {2007}
}
@inproceedings{faucris.228588999,
address = {ROCKVILLE},
author = {Berner, Daniel and Hoja, Ursula and Zenkel, Matthias and Pasutto, Francesca and Lee, Mei Chin and Aung, Tin and Khor, Chiea Chuen and Reis, André and Kruse, Friedrich and Schlötzer-Schrehardt, Ursula},
booktitle = {INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE},
date = {2019-04-28/2019-05-02},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-11-01},
peerreviewed = {unknown},
publisher = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
title = {{Functional} implication of the pseudoexfoliation-associated rare variant p.{Y407F} at {LOXL1}},
venue = {Vancouver},
year = {2019}
}
@article{faucris.205196517,
abstract = {Height is a complex quantitative trait with a high heritability. Short stature is diagnosed when height is significantly below the average of the general population for that person's age and sex. We have recently found that the retinoic acid degrading enzyme CYP26C1 modifies SHOX deficiency phenotypes toward more severe clinical manifestations. Here, we asked whether damaging variants in CYP26C1 alone could lead to short stature. We performed exome and Sanger sequencing to analyze 856 individuals with short stature where SHOX deficiency was previously excluded. Three different damaging missense variants and one splicing variant were identified in six independent individuals; the functional significance of the identified variants was tested in vitro or in vivo using zebrafish as a model. The genetic and functional data reported here indicate that CYP26C1 represents a novel gene underlying growth disorders and that damaging variants in the absence of SHOX variants can lead to short stature.},
author = {Montalbano, Antonino and Juergensen, Lonny and Fukami, Maki and Thiel, Christian and Hauer, Nadine and Roeth, Ralph and Weiss, Birgit and Naiki, Yasuhiro and Ogata, Tsutomu and Hassel, David and Rappold, Gudrun A.},
doi = {10.1038/s41431-018-0148-9},
faupublication = {yes},
journal = {European journal of human genetics},
note = {EVALuna2:34621},
pages = {1113-1120},
peerreviewed = {Yes},
title = {{Functional} missense and splicing variants in the retinoic acid catabolizing enzyme {CYP26C1} in idiopathic short stature},
volume = {26},
year = {2018}
}
@inproceedings{faucris.228300014,
address = {LONDON},
author = {Rappold, G. A. and Montalbano, A. and Juergensen, L. and Fukami, M. and Thiel, Christian and Hauer, Nadine and Roeth, R. and Weiss, B. and Naiki, Y. and Ogata, T. and Hassel, D.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2018-06-16/2018-06-19},
doi = {10.1038/s41431-018-0148-9},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {129-130},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{Functional} missense and splicing variants in the retinoic acid catabolizing enzyme {CYP26C1} in idiopathic short stature},
venue = {Milan, ITALY},
year = {2019}
}
@article{faucris.107196804,
abstract = {In patients with congenital heart defects, chromosomal anomalies are 100 times more frequent than in control subjects. Coarctation of the aorta can be detected in 15-20% of patients with Ullrich-Turner syndrome. By extensively reviewing literature involving breakpoint analysis of gonosomal deletions in Ullrich- Turner syndrome patients with and without coarctation of the aorta, we identified several gonosomal homolgous gene pairs of interest. Four of these homologous gene pairs were investigated by standard DNA sequencing in a cohort of 83 patients with non-syndromic coarctation of the aorta. Subsequently stability of mutant RNA and protein was analyzed to verify functional relevance of detected mutations. We identified two unreported missense mutations in Exon 8 (p.D69H) and 9 (p.R176W) of TBL1Y. Bioinformatic analysis and 3D modelling predicted that both mutations lead to TBL1Y loss of function. In RT-PCR and Western blot analyses of HEK293 cells transfected with a vector carrying the full-length TBL1Y (wild-type and mutant), we documented the predicted protein instability by showing protein decay for both mutant proteins. TBL1Y is similar to its gonosomal homologue, TBL1X, and its autosomal homologue, TBLR1, on chromosome 3. Both genes are part of co-repressor machineries and required for transcriptional activation by transcription factors that involve CtBP1/2, which contributes to Notch signaling. Several studies have shown that Notch signalling is important for proper development of the left ventricular outflow tract. Our findings suggest that TBL1Y is involved in the genesis of non-syndromic coarctation of the aorta.},
author = {Tagariello, Andreas and Breuer, C. and Birkner, Y. and Schmidt, Stefan and Koch, Anna Maria and Cesnjevar, Robert and Rueffer, A. and Dittrich, Sven and Schneider, H. and Winterpacht, Andreas and Sticht, Heinrich and Doetsch, J. and Toka, O.},
doi = {10.2174/156652412798889027},
faupublication = {yes},
journal = {Current Molecular Medicine},
note = {EVALuna2:9136},
pages = {199-205},
peerreviewed = {Yes},
title = {{Functional} null mutations in the gonosomal homologue gene {TBL1Y} are associated with non-syndromic coarctation of the aorta},
volume = {12},
year = {2012}
}
@article{faucris.277094617,
abstract = {While inherited hemizygous variants in PHF6 cause X-linked recessive Borjeson-Forssman-Lehmann syndrome (BFLS) in males, de novo heterozygous variants in females are associated with an overlapping but distinct phenotype, including moderate to severe intellectual disability, characteristic facial dysmorphism, dental, finger and toe anomalies, and linear skin pigmentation. By personal communication with colleagues, we assembled 11 additional females with BFLS due to variants in PHF6. We confirm the distinct phenotype to include variable intellectual disability, recognizable facial dysmorphism and other anomalies. We observed skewed X-inactivation in blood and streaky skin pigmentation compatible with functional mosaicism. Variants occurred de novo in 10 individuals, of whom one was only mildly affected and transmitted it to her more severely affected daughter. The mutational spectrum comprises a two-exon deletion, five truncating, one splice-site and three missense variants, the latter all located in the PHD2 domain and predicted to severely destabilize the domain structure. This observation supports the hypothesis of more severe variants in females contributing to gender-specific phenotypes in addition to or in combination with effects of X-inactivation and functional mosaicism. Therefore, our findings further delineate the clinical and mutational spectrum of female BFLS and provide further insights into possible genotype-phenotype correlations between females and males.},
author = {Gerber, Celine B. and Fliedner, Anna and Bartsch, Oliver and Berland, Siren and Dewenter, Malin and Haug, Marte and Hayes, Ian and Marin-Reina, Purificacion and Mark, Paul R. and Martinez-Castellano, Francisco and Maystadt, Isabelle and Karadurmus, Deniz and Steindl, Katharina and Wiesener, Antje and Zweier, Markus and Sticht, Heinrich and Zweier, Christiane},
doi = {10.1111/cge.14173},
faupublication = {yes},
journal = {Clinical Genetics},
keywords = {Borjeson-Forssman-Lehmann syndrome; de novo; PHF6; X-chromosomal},
note = {CRIS-Team WoS Importer:2022-06-24},
peerreviewed = {Yes},
title = {{Further} characterization of {Borjeson}-{Forssman}-{Lehmann} syndrome in females due to de novo variants in {PHF6}},
year = {2022}
}
@inproceedings{faucris.248101487,
address = {LONDON},
author = {Gumuslu, E. and Karaer, K. and Gumus, E. and Ekici, Arif Bülent and Kraus, Cornelia and Reis, André},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {862-863},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Further} clinical and molecular delineation of {Alazami} syndrome associated with variants in {LARP7}},
year = {2020}
}
@inproceedings{faucris.248099746,
address = {LONDON},
author = {Schuhmann, Sarah and Koller, H. and Sticht, Heinrich and Kraus, Cornelia and Krumbiegel, Mandy and Uebe, Steffen and Ekici, Arif Bülent and Reis, André and Thiel, C. T.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {841-841},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Further} clinical and molecular delineation of spondylocostal dysostosis type 3},
year = {2020}
}
@article{faucris.239155812,
abstract = {X-linked intellectual disability (XLID) is a genetically heterogeneous condition involving more than 100 genes. To date, 35 pathogenic variants have been reported in the lysine specific demethylase 5C (KDM5C) gene. KDM5C variants are one of the major causes of moderate to severe XLID. Affected males present with short stature, distinctive facial features, behavioral disorders, epilepsy, and spasticity. For most of these variants, related female carriers have been reported, but phenotypic descriptions were poor. Here, we present clinical and molecular features of 19 females carrying 10 novel heterozygous variants affecting KDM5C function, including five probands with de novo variants. Four heterozygous females were asymptomatic. All affected individuals presented with learning disabilities or ID (mostly moderate), and four also had a language impairment mainly affecting expression. Behavioral disturbances were frequent, and endocrine disorders were more frequent in females. In conclusion, our findings provide evidence of the role of KDM5C in ID in females highlighting the increasing implication of XLID genes in females, even in sporadic affected individuals. Disease expression of XLID in females should be taken into consideration for genetic counseling.},
author = {Carmignac, Virginie and Nambot, Sophie and Lehalle, Daphne and Callier, Patrick and Moortgat, Stephanie and Benoit, Valerie and Ghoumid, Jamal and Delobel, Bruno and Smol, Thomas and Thuillier, Caroline and Zordan, Cecile and Naudion, Sophie and Bienvenu, Thierry and Touraine, Renaud and Ramond, Francis and Zweier, Christiane and Reis, André and Kraus, Cornelia and Nizon, Mathilde and Cogne, Benjamin and Verloes, Alain and Tran Mau-Them, Frederic and Sorlin, Arthur and Jouan, Thibaud and Duffourd, Yannis and Tisserant, Emilie and Philippe, Christophe and Vitobello, Antonio and Thevenon, Julien and Faivre, Laurence and Thauvin-Robinet, Christel},
doi = {10.1111/cge.13755},
faupublication = {yes},
journal = {Clinical Genetics},
keywords = {data-sharing; exome; females; KDM5C; X-linked intellectual disability},
note = {CRIS-Team Scopus Importer:2020-06-09},
peerreviewed = {Yes},
title = {{Further} delineation of the female phenotype with {KDM5C} disease causing variants: 19 new individuals and review of the literature},
year = {2020}
}
@article{faucris.123156924,
abstract = {The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis of the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, are the most frequent cause of HSP. To understand how mutations in SPG4 affect human neurons, we generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of two patients carrying a c.1684C>T nonsense mutation and from two controls. These SPG4 and control hiPSCs were able to differentiate into neurons and glia at comparable efficiency. All known spastin isoforms were reduced in SPG4 neuronal cells. The complexity of SPG4 neurites was decreased, which was paralleled by an imbalance of axonal transport with less retrograde movement. Prominent neurite swellings with disrupted microtubules were present in SPG4 neurons at an ultrastructural level. While some of these swellings contain acetylated and detyrosinated tubulin, these tubulin modifications were unchanged in total cell lysates of SPG4 neurons. Upregulation of another microtubule-severing protein, p60 katanin, may partially compensate for microtubuli dynamics in SPG4 neurons. Overexpression of the M1 or M87 spastin isoforms restored neurite length, branching, numbers of primary neurites and reduced swellings in SPG4 neuronal cells. We conclude that neurite complexity and maintenance in HSP patient-derived neurons are critically sensitive to spastin gene dosage. Our data show that elevation of single spastin isoform levels is sufficient to restore neurite complexity and reduce neurite swellings in patient cells. Furthermore, our human model offers an ideal platform for pharmacological screenings with the goal to restore physiological spastin levels in SPG4 patients.},
author = {Havlicek, Steven and Kohl, Zacharias and Mishra, Himanshu Kumar and Prots, Iryna and Eberhardt, Esther and Denguir, Naime and Wend, Holger and Ploetz, Sonja and Boyer, Leah and Marchetto, Maria C. N. and Aigner, Stefan and Sticht, Heinrich and Groemer, Teja W. and Hehr, Ute and Lampert, Angelika and Schlötzer-Schrehardt, Ursula and Winkler, Jürgen and Gage, Fred H. and Winner, Beate},
doi = {10.1093/hmg/ddt644},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:2420},
pages = {2527-41},
peerreviewed = {Yes},
title = {{Gene} dosage-dependent rescue of {HSP} neurite defects in {SPG4} patients' neurons},
volume = {23},
year = {2014}
}
@article{faucris.259592825,
abstract = {Simple Summary},
author = {Park, Jooyong and Choi, Ji-Yeob and Choi, Jaesung and Chung, Seokang and Song, Nan and Park, Sue K. and Han, Wonshik and Noh, Dong-Young and Ahn, Sei-Hyun and Lee, Jong Won and Kim, Mi Kyung and Jee, Sun Ha and Wen, Wanqing and Bolla, Manjeet K. and Wang, Qin and Dennis, Joe and Michailidou, Kyriaki and Shah, Mitul and Conroy, Don M. and Harrington, Patricia A. and Mayes, Rebecca and Czene, Kamila and Hall, Per and Teras, Lauren R. and Patel, Alpa V. and Couch, Fergus J. and Olson, Janet E. and Sawyer, Elinor J. and Roylance, Rebecca and Bojesen, Stig E. and Flyger, Henrik and Lambrechts, Diether and Baten, Adinda and Matsuo, Keitaro and Ito, Hidemi and Guenel, Pascal and Truong, Therese and Keeman, Renske and Schmidt, Marjanka K. and Wu, Anna H. and Tseng, Chiu-Chen and Cox, Angela and Cross, Simon S. and Andrulis, Irene L. and Hopper, John L. and Southey, Melissa C. and Wu, Pei-Ei and Shen, Chen-Yang and Fasching, Peter and Ekici, Arif Bülent and Muir, Kenneth and Lophatananon, Artitaya and Brenner, Hermann and Arndt, Volker and Jones, Michael E. and Swerdlow, Anthony J. and Hoppe, Reiner and Ko, Yon-Dschun and Hartman, Mikael and Li, Jingmei and Mannermaa, Arto and Hartikainen, Jaana M. and Benitez, Javier and Gonzalez-Neira, Anna and Haiman, Christopher A. and Doerk, Thilo and Bogdanova, Natalia V. and Teo, Soo Hwang and Mohd Taib, Nur Aishah and Fletcher, Olivia and Johnson, Nichola and Grip, Mervi and Winqvist, Robert and Blomqvist, Carl and Nevanlinna, Heli and Lindblom, Annika and Wendt, Camilla and Kristensen, Vessela N. and Tollenaar, Rob A. E. M. and Heemskerk-Gerritsen, Bernadette A. M. and Radice, Paolo and Bonanni, Bernardo and Hamann, Ute and Manoochehri, Mehdi and Lacey, James V. and Martinez, Maria Elena and Dunning, Alison M. and Pharoah, Paul D. P. and Easton, Douglas F. and Yoo, Keun-Young and Kang, Daehee},
doi = {10.3390/cancers13102370},
faupublication = {yes},
journal = {Cancers},
note = {CRIS-Team WoS Importer:2021-06-04},
peerreviewed = {Yes},
title = {{Gene}-{Environment} {Interactions} {Relevant} to {Estrogen} and {Risk} of {Breast} {Cancer}: {Can} {Gene}-{Environment} {Interactions} {Be} {Detected} {Only} among {Candidate} {SNPs} from {Genome}-{Wide} {Association} {Studies}?},
volume = {13},
year = {2021}
}
@article{faucris.212414704,
abstract = {Breast and ovarian cancer (BC/OC) predisposition has been attributed to a number of high- and moderate to low-penetrance susceptibility genes. With the advent of next generation sequencing (NGS) simultaneous testing of these genes has become feasible. In this monocentric study, we report results of panel-based screening of 14 BC/OC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, CHEK2, PALB2, ATM, NBN, CDH1, TP53, MLH1, MSH2, MSH6 and PMS2) in a group of 581 consecutive individuals from a German population with BC and/or OC fulfilling diagnostic criteria for BRCA1 and BRCA2 testing including 179 with a triple-negative tumor. Altogether we identified 106 deleterious mutations in 105 (18%) patients in 10 different genes, including seven different exon deletions. Of these 106 mutations, 16 (15%) were novel and only six were found in BRCA1/2. To further characterize mutations located in or nearby splicing consensus sites we performed RT-PCR analysis which allowed confirmation of pathogenicity in 7 of 9 mutations analyzed. In PALB2, we identified a deleterious variant in six cases. All but one were associated with early onset BC and a positive family history indicating that penetrance for PALB2 mutations is comparable to BRCA2. Overall, extended testing beyond BRCA1/2 identified a deleterious mutation in further 6% of patients. As a downside, 89 variants of uncertain significance were identified highlighting the need for comprehensive variant databases. In conclusion, panel testing yields more accurate information on genetic cancer risk than assessing BRCA1/2 alone and wide-spread testing will help improve penetrance assessment of variants in these risk genes.},
author = {Kraus, Cornelia and Hoyer, Juliane and Vasileiou, Georgia and Wunderle, Marius and Lux, Michael P. and Fasching, Peter and Krumbiegel, Mandy and Uebe, Steffen and Reuter, Miriam and Beckmann, Matthias and Reis, André},
doi = {10.1002/ijc.30428},
faupublication = {yes},
journal = {International Journal of Cancer},
note = {EVALuna2:9340},
pages = {95-102},
peerreviewed = {Yes},
title = {{Gene} panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than {BRCA1}/2},
volume = {140},
year = {2017}
}
@article{faucris.274117772,
abstract = {Pathogenic bi-allelic variants in the SPG11 gene result in rare motor neuron disorders such as Hereditary Spastic Paraplegia type 11, Charcot-Marie Tooth, and Juvenile Amyotrophic Lateral Sclerosis-5. The main challenge in SPG11-linked disease research is the lack of antibodies against SPG11 encoded spatacsin. Here, we describe the CRISPR/Cas9 mediated generation and validation of an endogenously tagged SPG11- human iPSC line that contains an HA tag at the C-terminus of SPG11. The line exhibits multi-lineage differentiation potential and holds promise for studying the role of spatacsin and for the elucidation of SPG11-associated pathogenesis. Resource Table.},
author = {Winner, Beate and Krumm, Laura and Pozner, Tatyana and Kaindl, Johanna and Regensburger, Martin and Günther, Claudia and Turan, Sören and Asadollahi, Reza and Rauch, Anita},
doi = {10.1016/j.scr.2021.102520},
faupublication = {yes},
journal = {Stem Cell Research},
pages = {102520},
peerreviewed = {Yes},
title = {{Generation} and characterization of an endogenously tagged {SPG11}-human {iPSC} line by {CRISPR}/{Cas9} mediated knock-in},
url = {https://www.sciencedirect.com/science/article/pii/S1873506121003676?via=ihub},
volume = {56},
year = {2021}
}
@article{faucris.285408859,
abstract = {Aggregation of alpha-synuclein (aSyn) is closely linked to Parkinson's disease, probably due to the loss of physiological functions and/or gain of toxic functions of aggregated aSyn. Significant efforts have been made elucidating the physiological structure and function of aSyn, however, with limited success thus far in human -derived cells, partly because of restricted resources. Here, we developed two human-induced pluripotent stem cell lines using CRISPR/Cas9-mediated allele-specific frame-shift deletion of the aSyn encoding gene SNCA, resulting in homo-and heterozygous SNCA knockout. The generated cell lines are promising cellular tools for studying aSyn dosage-dependent functions and structural alterations in human neural cells.},
author = {Schneider, Yanni and Turan, Soeren and Koller, Aron and Krumbiegel, Mandy and Farrell, Michaela and Plotz, Sonja and Winkler, Jürgen and Xiang, Wei},
doi = {10.1016/j.scr.2022.102952},
faupublication = {yes},
journal = {Stem Cell Research},
note = {CRIS-Team WoS Importer:2022-11-18},
peerreviewed = {Yes},
title = {{Generation} of a homozygous and a heterozygous {SNCA} gene knockout human-induced pluripotent stem cell line by {CRISPR}/{Cas9} mediated allele-specific tuning of {SNCA} expression},
volume = {65},
year = {2022}
}
@article{faucris.267002056,
abstract = {Pathogenic bi-allelic variants in the SPG11 gene result in rare motor neuron disorders such as Hereditary Spastic Paraplegia type 11, Charcot-Marie Tooth, and Juvenile Amyotrophic Lateral Sclerosis-5. The main challenge in SPG11-linked disease research is the lack of antibodies against SPG11 encoded spatacsin. Here, we describe the CRISPR/Cas9 mediated generation and validation of an endogenously tagged SPG11- human iPSC line that contains an HA tag at the C-terminus of SPG11. The line exhibits multi-lineage differentiation potential and holds promise for studying the role of spatacsin and for the elucidation of SPG11-associated pathogenesis.},
author = {Krumm, Laura and Pozner, Tatyana and Kaindl, Johanna and Regensburger, Martin and Günther, Claudia and Turan, Sören and Asadollahi, Reza and Rauch, Anita and Winner, Beate},
doi = {10.1016/j.scr.2021.102520},
faupublication = {yes},
journal = {Stem Cell Research},
note = {CRIS-Team Scopus Importer:2021-09-10},
peerreviewed = {Yes},
title = {{Genetically} {Single} {Generation} and characterization of an endogenously tagged {SPG11}-human {iPSC} line by {CRISPR}/{Cas9} mediated knock-in},
volume = {56},
year = {2021}
}
@article{faucris.252998075,
author = {Haskamp, Stefan and Horowitz, Joseph and Oji, Vinzenz and Philipp, Sandra and Sticherling, Michael and Schäkel, Knut and Schuhmann, Sarah and Prinz, Jörg C. and Burkhardt, Harald and Behrens, Frank and Böhm, Beate and Köhm, Michaela and Rech, Jürgen and Simon, David and Schett, Georg and Morrison, Kirsten and Gerdes, Sascha and Assmann, Gunter and Nimeh, Ali and Schuster, Volker and Jacobi, Arnd and Weyergraf, Ansgar and Reis, André and Uebe, Steffen and Wilsmann-Theis, Dagmar and Mößner, Rotraut and Hüffmeier, Ulrike},
doi = {10.1016/j.jid.2021.01.017},
faupublication = {yes},
journal = {Journal of Investigative Dermatology},
note = {CRIS-Team Scopus Importer:2021-03-26},
peerreviewed = {Yes},
title = {{Genetic} {Analysis} of {MPO} {Variants} in {Four} {Psoriasis} {Subtypes} in {Patients} from {Germany}},
year = {2021}
}
@article{faucris.110917004,
abstract = {We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype-phenotype correlations.We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular and clinical data from patients with SYNGAP1 mutations from other centres were also collected, focusing on developmental aspects and the associated epilepsy phenotype. A review of SYNGAP1 mutations published in the literature was also performed.We describe 17 unrelated affected individuals carrying 13 different novel loss-of-function SYNGAP1 mutations. Developmental delay was the first manifestation of SYNGAP1-related encephalopathy; intellectual disability became progressively obvious and was associated with autistic behaviours in eight patients. Hypotonia and unstable gait were frequent associated neurological features. With the exception of one patient who experienced a single seizure, all patients had epilepsy, characterised by falls or head drops due to atonic or myoclonic seizures, (myoclonic) absences and/or eyelid myoclonia. Triggers of seizures were frequent (n=7). Seizures were pharmacoresistant in half of the patients. The severity of the epilepsy did not correlate with the presence of autistic features or with the severity of cognitive impairment. Mutations were distributed throughout the gene, but spared spliced 3' and 5' exons. Seizures in patients with mutations in exons 4-5 were more pharmacoresponsive than in patients with mutations in exons 8-15.SYNGAP1 encephalopathy is characterised by early neurodevelopmental delay typically preceding the onset of a relatively recognisable epilepsy comprising generalised seizures (absences, myoclonic jerks) and frequent triggers.},
author = {Mignot, Cyril and Von Stuelpnagel, Celina and Nava, Caroline and Ville, Dorothee and Sanlaville, Damien and Lesca, Gaetan and Rastetter, Agnes and Gachet, Benoit and Marie, Yannick and Korenke, G. Christoph and Borggraefe, Ingo and Hoffmann-Zacharska, Dorota and Szczepanik, Elzbieta and Rudzka-Dybala, Mariola and Yis, Uluc and Caglayan, Hande and Isapof, Arnaud and Marey, Isabelle and Panagiotakaki, Eleni and Korff, Christian and Rossier, Eva and Riess, Angelika and Beck-Woedl, Stefanie and Rauch, Anita and Zweier, Christiane and Hoyer, Juliane and Reis, André and Mironov, Mikhail and Bobylova, Maria and Mukhin, Konstantin and Hernandez-Hernandez, Laura and Maher, Bridget and Sisodiya, Sanjay and Kuhn, Marius and Glaeser, Dieter and Wechuysen, Sarah and Myers, Candace T. and Mefford, Heather C. and Hoertnagel, Konstanze and Biskup, Saskia and Lemke, Johannes R. and Heron, Delphine and Kluger, Gerhard and Depienne, Christel},
doi = {10.1136/jmedgenet-2015-103451},
faupublication = {yes},
journal = {Journal of Medical Genetics},
note = {EVALuna2:9321},
pages = {511-22},
peerreviewed = {Yes},
title = {{Genetic} and neurodevelopmental spectrum of {SYNGAP1}-associated intellectual disability and epilepsy},
volume = {53},
year = {2016}
}
@article{faucris.123880724,
abstract = {Large-scale genotyping studies have identified over 70 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. However, knowledge regarding genetic risk factors associated with the prognosis is limited. The aim of this study was therefore to investigate the prognostic effect of nine known breast cancer risk SNPs. BC patients (n = 1687) randomly sampled in an adjuvant, randomized phase III trial (SUCCESS A study) were genotyped for nine BC risk SNPs: rs17468277 (CASP8) , rs2981582 (FGFR2) , rs13281615(8q24), rs3817198 (LSP1) , rs889312 (MAP3K1) , rs3803662 (TOX3) , rs13387042(2q35), rs4973768 (SLC4A7) , rs6504950 (COX11) . Cox proportional hazards models were used to test the SNPs' association with overall survival (OS) and progression-free survival (PFS). Additional analyses were carried out for molecular subgroups. rs3817198 in LSP1 (lymphocyte-specific protein 1) was the only SNP that significantly influenced OS (p = 0.01) and PFS (p < 0.01) in the likelihood ratio test comparing the genetic survival model with the clinical survival model. In the molecular subgroups, triple-negative patients with two minor alleles in rs3817198 had a much better prognosis relative to OS (adjusted HR 0.03; 95% CI 0.002 - 0.279) and PFS (HR 0.09; 95% CI 0.02 - 0.36) than patients with the common alleles. The same effect on PFS was shown for patients with luminal A tumors (HR 0.19; 95% CI 0.05 - 0.84), whereas patients with luminal B tumors had a poorer PFS with two minor alleles (HR 2.13; 95% CI 1.02 - 4.40). The variant in rs3817198 has a prognostic effect particularly in the subgroup of patients with triple-negative BC, suggesting a possible link with immunomodulation and BC.},
author = {Hein, Alexander and Rack, B. and Li, L. and Ekici, Arif Bülent and Reis, André and Lux, Michael P. and Cunningham, J. M. and Rübner, Matthias and Fridley, B. L. and Schneeweiss, A. and Tesch, H. and Lichtenegger, W. and Fehm, T. and Heinrich, G. and Rezai, M. and Beckmann, Matthias and Janni, W. and Weinshilboum, R. M. and Wang, L. and Fasching, Peter and Haeberle, L.},
doi = {10.1055/s-0042-113189},
faupublication = {yes},
journal = {Geburtshilfe und Frauenheilkunde},
note = {EVALuna2:9355},
pages = {651-659},
peerreviewed = {Yes},
title = {{Genetic} {Breast} {Cancer} {Susceptibility} {Variants} and {Prognosis} in the {Prospectively} {Randomized} {SUCCESS} {A} {Study}},
volume = {77},
year = {2017}
}
@inproceedings{faucris.266503326,
address = {HOBOKEN},
author = {De Moraes, Helena Tadiello and Urquia-Osorio, Hebel and Cavalcante, Charlington M. and Guerreiro, Marilisa M. and Montenegro, Maria Augusta and Coan, Ana Carolina and Medina, Marco T. and Caraballo, Roberto and Wiesmann da Silva Reis, André and Thiel, Christian and Uebe, Steffen and Lopes-Cendes, Iscia},
booktitle = {EPILEPSIA},
date = {2021-08-28/2021-09-01},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-11-26},
pages = {212-213},
peerreviewed = {unknown},
publisher = {WILEY},
title = {{Genetic} diagnostic yield in a large cohort of patients with developmental and epileptic encephalopathy from {Latin} {America}: a preliminary report},
year = {2021}
}
@article{faucris.233229038,
abstract = {Neurodevelopmental disorders (NDDs) are clinically and genetically extremely heterogeneous with shared phenotypes often associated with genes from the same networks. Mutations in TCF4, MEF2C, UBE3A, ZEB2 or ATRX cause phenotypically overlapping, syndromic forms of NDDs with severe intellectual disability, epilepsy and microcephaly. To characterize potential functional links between these genes/proteins, we screened for genetic interactions in Drosophila melanogaster. We induced ubiquitous or tissue specific knockdown or overexpression of each single orthologous gene (Da, Mef2, Ube3a, Zfh1, XNP) and in pairwise combinations. Subsequently, we assessed parameters such as lethality, wing and eye morphology, neuromuscular junction morphology, bang sensitivity and climbing behaviour in comparison between single and pairwise dosage manipulations. We found most stringent evidence for genetic interaction between Ube3a and Mef2 as simultaneous dosage manipulation in different tissues including glia, wing and eye resulted in multiple phenotype modifications. We subsequently found evidence for physical interaction between UBE3A and MEF2C also in human cells. Systematic pairwise assessment of the Drosophila orthologues of five genes implicated in clinically overlapping, severe NDDs and subsequent confirmation in a human cell line revealed interactions between UBE3A/Ube3a and MEF2C/Mef2, thus contributing to the characterization of the underlying molecular commonalities.},
author = {Straub, Jonas and Gregor, Anne and Sauerer, Tatjana and Fliedner, Anna and Distel, Luitpold and Suchy, Christine and Ekici, Arif Bülent and Ferrazzi, Fulvia and Zweier, Christiane},
doi = {10.1038/s41598-020-58182-5},
faupublication = {yes},
journal = {Scientific Reports},
note = {CRIS-Team Scopus Importer:2020-02-04},
peerreviewed = {Yes},
title = {{Genetic} interaction screen for severe neurodevelopmental disorders reveals a functional link between {Ube3a} and {Mef2} in {Drosophila} melanogaster},
volume = {10},
year = {2020}
}
@inproceedings{faucris.228295112,
address = {LONDON},
author = {Straub, Jonas and Sauerer, Tatjana and Fliedner, Anna and Distel, Luitpold and Suchy, C. and Ekici, Arif Bülent and Ferrazzi, Fulvia and Gregor, Anne and Zweier, Christiane},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2019-06-15/2019-06-18},
doi = {10.1038/s41598-020-58182-5},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {1399-1399},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{Genetic} {Interaction} screen for severe neurodevelopmental disorders reveals a functional link between {Ube3a} and {Mef2} in {Drosophila} melanogaster},
venue = {Gothenburg, SWEDEN},
year = {2019}
}
@article{faucris.223998704,
abstract = {Objective: To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. Design: Genome-wide association study. Setting: Not applicable. Patient(s): Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded. Intervention(s): None. Main Outcome Measure(s): The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status. Result(s): The median age of the 1,168 women was 41 years (range 19–45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5′ upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation. Conclusion(s): Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer.},
author = {Ruddy, Kathryn J. and Schaid, Daniel J. and Partridge, A. H. and Larson, Nicholas B. and Batzler, Anthony and Häberle, Lothar and Dittrich, Ralf and Widschwendter, P. and Fink, Visnja and Bauer, Emanuel and Schwitulla, Judith and Rübner, Matthias and Ekici, Arif Bülent and Aivazova-Fuchs, Viktoria and Stewart, Elizabeth A. and Beckmann, Matthias and Ginsburg, Elizabeth and Wang, Liewei and Weinshilboum, Richard M. and Couch, Fergus J. and Janni, Wolfgang and Rack, Brigitte and Vachon, Celine and Fasching, Peter},
doi = {10.1016/j.fertnstert.2019.05.018},
faupublication = {yes},
journal = {Fertility and Sterility},
keywords = {amenorrhea; Breast neoplasms; drug therapy; toxicity},
note = {CRIS-Team Scopus Importer:2019-08-06},
peerreviewed = {Yes},
title = {{Genetic} predictors of chemotherapy-related amenorrhea in women with breast cancer},
year = {2019}
}
@article{faucris.106288644,
abstract = {Short stature is a common pediatric disorder affecting 3% of the population. However, the clinical variability and genetic heterogeneity prevents the identification of the underlying cause in about 80% of the patients. Recently, heterozygous mutations in the ACAN gene coding for the proteoglycan aggrecan, a main component of the cartilage matrix, were associated with idiopathic short stature. To ascertain the prevalence of ACAN mutations and broaden the phenotypic spectrum in patients with idiopathic short stature we performed sequence analyses in 428 families. We identified heterozygous nonsense mutations in four and potentially disease-causing missense variants in two families (1.4%). These patients presented with a mean of -3.2 SDS and some suggestive clinical characteristics. The results suggest heterozygous mutations in ACAN as a common cause of isolated as well as inherited idiopathic short stature.},
author = {Hauer, Nadine and Sticht, Heinrich and Boppudi, Sangamitra and Büttner, Christian and Kraus, Cornelia and Trautmann, Udo and Zenker, Martin and Zweier, Christiane and Wiesener, Antje and Abou Jamra, Rami and Wieczorek, Dagmar and Kelkel, Jaqueline and Jung, Anna-Maria and Uebe, Steffen and Ekici, Arif Bülent and Rohrer, Tilman and Reis, André and Dörr, Helmuth-Günther and Thiel, Christian},
doi = {10.1038/s41598-017-12465-6},
faupublication = {yes},
journal = {Scientific Reports},
note = {EVALuna2:9379},
pages = {12225},
peerreviewed = {Yes},
title = {{Genetic} screening confirms heterozygous mutations in {ACAN} as a major cause of idiopathic short stature},
volume = {7},
year = {2017}
}
@article{faucris.305613350,
abstract = {The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the transporters NaDC3 (SLC13A3) and ASBT (SLC10A2). Shared genetic determinants of 7,073 metabolite–disease combinations represent a resource to better understand metabolic diseases and revealed connections of dipeptidase 1 with circulating digestive enzymes and with hypertension. Extending genetic studies of the metabolome beyond plasma yields unique insights into processes at the interface of body compartments.},
author = {Schlosser, Pascal and Scherer, Nora and Grundner-Culemann, Franziska and Monteiro-Martins, Sara and Haug, Stefan and Steinbrenner, Inga and Uluvar, Burulça and Wuttke, Matthias and Cheng, Yurong and Ekici, Arif Bülent and Gyimesi, Gergely and Karoly, Edward D. and Kotsis, Fruzsina and Mielke, Johanna and Gomez, Maria F. and Yu, Bing and Grams, Morgan E. and Coresh, Josef and Boerwinkle, Eric and Köttgen, Michael and Kronenberg, Florian and Meiselbach, Heike and Mohney, Robert P. and Akilesh, Shreeram and Schmidts, Miriam and Hediger, Matthias A. and Schultheiss, Ulla T. and Eckardt, Kai-Uwe and Oefner, Peter J. and Sekula, Peggy and Li, Yong and Köttgen, Anna},
doi = {10.1038/s41588-023-01409-8},
faupublication = {yes},
journal = {Nature Genetics},
note = {CRIS-Team Scopus Importer:2023-06-16},
peerreviewed = {Yes},
title = {{Genetic} studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine},
year = {2023}
}
@inproceedings{faucris.265056814,
address = {ROCKVILLE},
author = {Clahsen, Thomas and Büttner, Christian and Hatami, Niloofar and Nuest, Felix and Gabriel, Tim and Reis, André and Cursiefen, Claus},
booktitle = {INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-10-15},
peerreviewed = {unknown},
publisher = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
title = {{Genetic} variability of lymphangiogenesis in {Collaborative} {Cross} mice: a powerful tool to identify novel endogenous regulators of lymphangiogenesis},
year = {2021}
}
@article{faucris.116819164,
abstract = {Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (~40 kb) in 50 indigenous, black South African XFS cases and 50 matched controls. The variants with the strongest evidence of association were located in a well-defined 7-kb region bounded by the 3'-end of exon 1 and the adjacent region of intron 1 of LOXL1. We replicated this finding in US Caucasian (91 cases/1031 controls), German (771 cases/1365 controls) and Japanese (1484 cases/1188 controls) populations. The region of peak association lies upstream of LOXL1-AS1, a long non-coding RNA (lncRNA) encoded on the opposite strand of LOXL1. We show that this region contains a promoter and, importantly, that the strongly associated XFS risk alleles in the South African population are functional variants that significantly modulate the activity of this promoter. LOXL1-AS1 expression is also significantly altered in response to oxidative stress in human lens epithelial cells and in response to cyclic mechanical stress in human Schlemm's canal endothelial cells. Taken together, these findings support a functional role for the LOXL1-AS1 lncRNA in cellular stress response and suggest that dysregulation of its expression by genetic risk variants plays a key role in XFS pathogenesis.},
author = {Hauser, Michael A. and Aboobakar, Inas F. and Liu, Yutao and Miura, Shiroh and Whigham, Benjamin T. and Challa, Pratap and Wheeler, Joshua and Williams, Andrew and Santiago-Turla, Cecelia and Qin, Xuejun and Rautenbach, Robyn M. and Ziskind, Ari and Ramsay, Michele and Uebe, Steffen and Song, Lingyun and Safi, Alexias and Vithana, Eranga N. and Mizoguchi, Takanori and Nakano, Satoko and Kubota, Toshiaki and Hayashi, Ken and Manabe, Shin-Ichi and Kazama, Shigeyasu and Mori, Yosai and Miyata, Kazunori and Yoshimura, Nagahisa and Reis, André and Crawford, Gregory E. and Pasutto, Francesca and Carmichael, Trevor R. and Williams, Susan E. I. and Ozaki, Mineo and Aung, Tin and Khor, Chiea-Chuen and Stamer, W. Daniel and Ashley-Koch, Allison E. and Allingham, R. Rand},
doi = {10.1093/hmg/ddv347},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:9211},
pages = {6552-63},
peerreviewed = {Yes},
title = {{Genetic} variants and cellular stressors associated with exfoliation syndrome modulate promoter activity of a {lncRNA} within the {LOXL1} locus},
volume = {24},
year = {2015}
}
@article{faucris.238589661,
abstract = {BACKGROUND: Syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic recurrent multifocal osteomyelitis (CRMO) present two diseases of a dermatologic and rheumatologic spectrum that are variable in manifestation und therapeutic response. Genetic risk factors have long been assumed in both diseases, but no single reliable factor has been identified yet. Therefore, we aimed to clinically characterize a patient group with syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) (n = 47) and chronic recurrent multifocal osteomyelitis (CRMO)/ chronic non-bacterial osteomyelitis (CNO) (n = 9) and analyze a CRMO candidate gene. METHODS: Clinical data of all patients were collected and assessed for different combinations of clinical symptoms. SAPHO patients were grouped into categories according to the acronym; disease-contribution by pathogens was evaluated. We sequenced coding exons of FBLIM1. RESULTS: Palmoplantar pustular psoriasis (PPP) was the most common skin manifestation in CRMO/CNO and SAPHO patients; most SAPHO patients had sterno-costo-clavicular hyperostosis. The most common clinical category of the acronym was S{\_}PHO (n = 26). Lack of pathogen detection from bone biopsies was more common than microbial isolation. We did not identify autosomal-recessive FBLIM1 variants. CONCLUSIONS: S{\_}PHO is the most common combination of symptoms of its acronym. Genetic analyses of FBLIM1 did not provide evidence that this gene is relevant in our patient group. Our study indicates the need to elucidate SAPHO's and CRMO/CNO's pathogenesis.},
author = {Assmann, Gunter and Köhm, Michaela and Schuster, Volker and Behrens, Frank and Mössner, Rotraut and Magnolo, Nina and Oji, Vinzenz and Burkhardt, Harald and Hüffmeier, Ulrike},
doi = {10.1186/s12881-020-01037-7},
faupublication = {yes},
journal = {Bmc Medical Genetics},
keywords = {Association; Chronic non-bacterial osteomyelitis (CNO); Chronic recurrent multifocal osteomyelitis (CRMO); Coding variants; Syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO (syndrome))},
note = {CRIS-Team Scopus Importer:2020-05-22},
pages = {102-},
peerreviewed = {Yes},
title = {{Genetic} variants in {FBLIM1} gene do not contribute to {SAPHO} syndrome and chronic recurrent multifocal osteomyelitis in typical patient groups},
volume = {21},
year = {2020}
}
@article{faucris.261052912,
abstract = {The extensive clinical and genetic heterogeneity of congenital limb malformation calls for comprehensive genome-wide analysis of genetic variation. Genome sequencing (GS) has the potential to identify all genetic variants. Here we aim to determine the diagnostic potential of GS as a comprehensive one-test-for-all strategy in a cohort of undiagnosed patients with congenital limb malformations. We collected 69 cases (64 trios, 1 duo, 5 singletons) with congenital limb malformations with no molecular diagnosis after standard clinical genetic testing and performed genome sequencing. We also developed a framework to identify potential noncoding pathogenic variants. We identified likely pathogenic/disease-associated variants in 12 cases (17.4%) including four in known disease genes, and one repeat expansion in HOXD13. In three unrelated cases with ectrodactyly, we identified likely pathogenic variants in UBA2, establishing it as a novel disease gene. In addition, we found two complex structural variants (3%). We also identified likely causative variants in three novel high confidence candidate genes. We were not able to identify any noncoding variants. GS is a powerful strategy to identify all types of genomic variants associated with congenital limb malformation, including repeat expansions and complex structural variants missed by standard diagnostic approaches. In this cohort, no causative noncoding SNVs could be identified.},
author = {Elsner, Jonas and Mensah, Martin A. and Holtgrewe, Manuel and Hertzberg, Jakob and Bigoni, Stefania and Busche, Andreas and Coutelier, Marie and de Silva, Deepthi C. and Elçioglu, Nursel and Filges, Isabel and Gerkes, Erica and Girisha, Katta M. and Graul-Neumann, Luitgard and Jamsheer, Aleksander and Krawitz, Peter and Kurth, Ingo and Markus, Susanne and Megarbane, Andre and Reis, André and Reuter, Miriam and Svoboda, Daniel and Teller, Christopher and Tuysuz, Beyhan and Türkmen, Seval and Wilson, Meredith and Woitschach, Rixa and Vater, Inga and Caliebe, Almuth and Hülsemann, Wiebke and Horn, Denise and Mundlos, Stefan and Spielmann, Malte},
doi = {10.1007/s00439-021-02295-y},
faupublication = {yes},
journal = {Human genetics},
note = {CRIS-Team Scopus Importer:2021-07-02},
peerreviewed = {Yes},
title = {{Genome} sequencing in families with congenital limb malformations},
year = {2021}
}
@article{faucris.123905804,
abstract = {Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 × 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.},
author = {Stuart, Philip E. and Nair, Rajan P. and Tsoi, Lam C. and Tejasvi, Trilokraj and Das, Sayantan and Kang, Hyun Min and Ellinghaus, Eva and Chandran, Vinod and Callis-Duffin, Kristina and Ike, Robert and Li, Yanming and Wen, Xiaoquan and Enerback, Charlotta and Gudjonsson, Johann E. and Koks, Sulev and Kingo, Kuelli and Esko, Tonu and Mrowietz, Ulrich and Reis, André and Wichmann, H. Erich and Gieger, Christian and Hoffmann, Per and Noethen, Markus M. and Winkelmann, Juliane and Kunz, Manfred and Moreta, Elvia G. and Mease, Philip J. and Ritchlin, Christopher T. and Bowcock, Anne M. and Krueger, Gerald G. and Lim, Henry W. and Weidinger, Stephan and Weichenthal, Michael and Voorhees, John J. and Rahman, Proton and Gregersen, Peter K. and Franke, Andre and Gladman, Dafna D. and Abecasis, Goncalo R. and Elder, James T.},
doi = {10.1016/j.ajhg.2015.10.019},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9293},
pages = {816-36},
peerreviewed = {Yes},
title = {{Genome}-wide {Association} {Analysis} of {Psoriatic} {Arthritis} and {Cutaneous} {Psoriasis} {Reveals} {Differences} in {Their} {Genetic} {Architecture}},
volume = {97},
year = {2015}
}
@article{faucris.118490284,
abstract = {Psoriatic Arthritis (PsA) is a chronic inflammatory disease of the joints. PsA is etiologically complex, and 11 susceptibility loci have been identified so far. Most of these overlap with loci associated with psoriasis vulgaris (PsV), the most common psoriatic skin manifestation which is also frequently seen in PsA patients. In addition, two copy number variants (CNVs) are associated with PsV, one of which, located within the LCE3 gene cluster, is also associated with PsA. Finally, an intergenic deletion has been reported as a PsA-specific CNV.We performed a genome-wide association study (GWAS) of CNVs in PsA and assessed the contribution to disease risk by CNVs at known psoriasis susceptibility loci.After stringent quality assessment and validation of CNVs of the GWAS with an alternative quantitative method, two significantly associated CNVs remained, one near UXS1, the other one at the TRB locus. However, MLPA analysis did not confirm the CN state in ~1/3 of individuals, and an analysis of an independent case-control-study failed to confirm the initial associations. Furthermore, detailed PCR-based analysis of the sequence at TRB revealed the existence of a more complex genomic sequence most accurately represented by freeze hg18 which accordingly failed to confirm the hg19 sequence. Only rare CNVs were detected at psoriasis susceptibility loci. At three of 12 susceptibility loci with CNVs (CSMD1, IL12B, RYR2), CN variability was confirmed independently by MLPA. Overall, the rate of CNV confirmation by MLPA was strongly dependent upon CNV type, CNV size and the number of array markers involved in a CNV.Although we identified PsA associations at several loci and confirmed that the common CNVs at these sites were real, ~1/3 of the common CNV states could not be reproduced. Furthermore, replication analysis failed to confirm the original association. Furthermore, SNP array-based analyses of CNVs were found to be more reliable for deletions than duplications, independent of the respective CNV allele frequency. CNVs are thus good candidate disease variants, while the methods to detect them should be applied cautiously and reproduced by an independent method.},
author = {Uebe, Steffen and Ehrlicher, Maria and Ekici, Arif Bülent and Behrens, Frank and Boehm, Beate and Homuth, Georg and Schurmann, Claudia and Voelker, Uwe and Juenger, Michael and Nauck, Matthias and Voelzke, Henry and Traupe, Heiko and Krawczak, Michael and Burkhardt, Harald and Reis, André and Hüffmeier, Ulrike},
doi = {10.1186/s12881-017-0447-y},
faupublication = {yes},
journal = {Bmc Medical Genetics},
note = {EVALuna2:9358},
pages = {92},
peerreviewed = {Yes},
title = {{Genome}-wide association and targeted analysis of copy number variants with psoriatic arthritis in {German} patients},
volume = {18},
year = {2017}
}
@article{faucris.119545624,
abstract = {Genetic and nongenetic factors contribute to development of pseudoexfoliation (PEX) syndrome, a complex, age-related, generalized matrix process frequently associated with glaucoma. To identify specific genetic variants underlying its etiology, we performed a genome-wide association study (GWAS) using a DNA-pooling approach. Therefore, equimolar amounts of DNA samples of 80 subjects with PEX syndrome, 80 with PEX glaucoma (PEXG) and 80 controls were combined into separate pools and hybridized to 500K SNP arrays (Affymetrix). Array probe intensity data were analyzed and visualized with expressly developed software tools GPFrontend and GPGraphics in combination with GenePool software. For replication, independent German cohorts of 610 unrelated patients with PEX/PEXG and 364 controls as well as Italian cohorts of 249 patients and 190 controls were used. Of 19, 17 SNPs showing significant allele frequency difference in DNA pools were confirmed by individual genotyping. Further single genotyping at CNTNAP2 locus revealed association between PEX/PEXG for two SNPs, which was confirmed in an independent German but not the Italian cohort. Both SNPs remained significant in the combined German cohorts even after Bonferroni correction (rs2107856: P(c)=0.0108, rs2141388: P(c)=0.0072). CNTNAP2 was found to be ubiquitously expressed in all human ocular tissues, particularly in retina, and localized to cell membranes of epithelial, endothelial, smooth muscle, glial and neuronal cells. Confirming efficiency of GWAS with DNA-pooling approach by detection of the known LOXL1 locus, our study data show evidence for association of CNTNAP2 with PEX syndrome and PEXG in German patients.},
author = {Krumbiegel, Mandy and Pasutto, Francesca and Schlötzer-Schrehardt, Ursula and Uebe, Steffen and Zenkel, Matthias and Mardin, Christian Y. and Weisschuh, Nicole and Paoli, Daniela and Gramer, Eugen and Becker, Christian and Ekici, Arif Bülent and Weber, Bernhard H. F. and Nuernberg, Peter and Kruse, Friedrich and Reis, André},
doi = {10.1038/ejhg.2010.144},
faupublication = {yes},
journal = {European journal of human genetics},
note = {EVALuna2:9084},
pages = {186-93},
peerreviewed = {Yes},
title = {{Genome}-wide association study with {DNA} pooling identifies variants at {CNTNAP2} associated with pseudoexfoliation syndrome},
volume = {19},
year = {2011}
}
@article{faucris.240994086,
abstract = {Invasion, metastasis and therapy resistance are the major cause of cancer-associated deaths, and the EMT-inducing transcription factor ZEB1 is a crucial stimulator of these processes. While work on ZEB1 has mainly focused on its role as a transcriptional repressor, it can also act as a transcriptional activator. To further understand these two modes of action, we performed a genome-wide ZEB1 binding study in triple-negative breast cancer cells. We identified ZEB1 as a novel interactor of the AP-1 factors FOSL1 and JUN and show that, together with the Hippo pathway effector YAP, they form a transactivation complex, predominantly activating tumour-promoting genes, thereby synergising with its function as a repressor of epithelial genes. High expression of ZEB1, YAP, FOSL1 and JUN marks the aggressive claudin-low subtype of breast cancer, indicating the translational relevance of our findings. Thus, our results link critical tumour-promoting transcription factors: ZEB1, AP-1 and Hippo pathway factors. Disturbing their molecular interaction may provide a promising treatment option for aggressive cancer types.},
author = {Feldker, Nora and Ferrazzi, Fulvia and Schuhwerk, Harald and Widholz, Sebastian A. and Guenther, Kerstin and Frisch, Isabell and Jakob, Kathrin and Kleemann, Julia and Riegel, Dania and Bönisch, Ulrike and Lukassen, Sören and Eccles, Rebecca and Schmidl, Christian and Stemmler, Marc and Brabletz, Thomas and Brabletz, Simone},
doi = {10.15252/embj.2019103209},
faupublication = {yes},
journal = {EMBO Journal},
keywords = {AP-1; breast cancer; epithelial to mesenchymal transition; ZEB1},
note = {CRIS-Team Scopus Importer:2020-07-31},
peerreviewed = {Yes},
title = {{Genome}-wide cooperation of {EMT} transcription factor {ZEB1} with {YAP} and {AP}-1 in breast cancer},
year = {2020}
}
@article{faucris.243058154,
abstract = {Invasion, metastasis and therapy resistance are the major cause of cancer-associated deaths, and theEMT-inducing transcription factorZEB1 is a crucial stimulator of these processes. While work onZEB1 has mainly focused on its role as a transcriptional repressor, it can also act as a transcriptional activator. To further understand these two modes of action, we performed a genome-wideZEB1 binding study in triple-negative breast cancer cells. We identifiedZEB1 as a novel interactor of theAP-1 factorsFOSL1 andJUNand show that, together with the Hippo pathway effectorYAP, they form a transactivation complex, predominantly activating tumour-promoting genes, thereby synergising with its function as a repressor of epithelial genes. High expression ofZEB1,YAP,FOSL1 andJUNmarks the aggressive claudin-low subtype of breast cancer, indicating the translational relevance of our findings. Thus, our results link critical tumour-promoting transcription factors:ZEB1,AP-1 and Hippo pathway factors. Disturbing their molecular interaction may provide a promising treatment option for aggressive cancer types.},
author = {Feldker, Nora and Ferrazzi, Fulvia and Schuhwerk, Harald and Widholz, Sebastian A. and Guenther, Kerstin and Frisch, Isabell and Jakob, Kathrin and Kleemann, Julia and Riegel, Dania and Boenisch, Ulrike and Lukassen, Sören and Eccles, Rebecca and Schmidl, Christian and Stemmler, Marc and Brabletz, Thomas and Brabletz, Simone},
faupublication = {yes},
journal = {EMBO Journal},
note = {CRIS-Team WoS Importer:2020-09-25},
peerreviewed = {Yes},
title = {{Genome}-wide cooperation {ofEMTtranscription} {factorZEB1} {withYAPandAP}-1 in breast cancer},
volume = {39},
year = {2020}
}
@article{faucris.265069771,
abstract = {Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 x 10(-8) and 4.42 x 10(-8)). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.},
author = {Escala-Garcia, Maria and Canisius, Sander and Keeman, Renske and Beesley, Jonathan and Anton-Culver, Hoda and Arndt, Volker and Augustinsson, Annelie and Becher, Heiko and Beckmann, Matthias and Behrens, Sabine and Bermisheva, Marina and Bojesen, Stig E. and Bolla, Manjeet K. and Brenner, Hermann and Canzian, Federico and Castelao, Jose E. and Chang-Claude, Jenny and Chanock, Stephen J. and Couch, Fergus J. and Czene, Kamila and Daly, Mary B. and Dennis, Joe and Devilee, Peter and Dork, Thilo and Dunning, Alison M. and Easton, Douglas F. and Ekici, Arif Bülent and Eliassen, A. Heather and Fasching, Peter and Flyger, Henrik and Gago-Dominguez, Manuela and Garcia-Closas, Montserrat and Garcia-Saenz, Jose A. and Geisler, Juergen and Giles, Graham G. and Grip, Mervi and Guendert, Melanie and Hahnen, Eric and Haiman, Christopher A. and Hakansson, Niclas and Hall, Per and Hamann, Ute and Hartikainen, Jaana M. and Heemskerk-Gerritsen, Bernadette A. M. and Hollestelle, Antoinette and Hoppe, Reiner and Hopper, John L. and Hunter, David J. and Jacot, William and Jakubowska, Anna and John, Esther M. and Jung, Audrey Y. and Kaaks, Rudolf and Khusnutdinova, Elza and Koppert, Linetta B. and Kraft, Peter and Kristensen, Vessela N. and Kurian, Allison W. and Lambrechts, Diether and Le Marchand, Loic and Lindblom, Annika and Luben, Robert N. and Lubinski, Jan and Mannermaa, Arto and Manoochehri, Mehdi and Margolin, Sara and Mavroudis, Dimitrios and Muranen, Taru A. and Nevanlinna, Heli and Olshan, Andrew F. and Olsson, Hakan and Park-Simon, Tjoung-Won and Patel, Alpa V. and Peterlongo, Paolo and Pharoah, Paul D. P. and Punie, Kevin and Radice, Paolo and Rennert, Gad and Rennert, Hedy S. and Romero, Atocha and Roylance, Rebecca and Ruediger, Thomas and Rübner, Matthias and Saloustros, Emmanouil and Sawyer, Elinor J. and Schmutzler, Rita K. and Schoemaker, Minouk J. and Scott, Christopher and Southey, Melissa C. and Surowy, Harald and Swerdlow, Anthony J. and Tamimi, Rulla M. and Teras, Lauren R. and Thomas, Emilie and Tomlinson, Ian and Troester, Melissa A. and Vachon, Celine M. and Wang, Qin and Winqvist, Robert and Wolk, Alicja and Ziogas, Argyrios and Michailidou, Kyriaki and Chenevix-Trench, Georgia and Bachelot, Thomas and Schmidt, Marjanka K.},
doi = {10.1038/s41598-021-99409-3},
faupublication = {yes},
journal = {Scientific Reports},
note = {CRIS-Team WoS Importer:2021-10-15},
peerreviewed = {Yes},
title = {{Germline} variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis},
volume = {11},
year = {2021}
}
@article{faucris.252874737,
abstract = {Objective: Mutations in the spastic paraplegia gene 11 (SPG11), encoding spatacsin, cause the most frequent form of autosomal-recessive complex hereditary spastic paraplegia (HSP) and juvenile-onset amyotrophic lateral sclerosis (ALS5). When SPG11 is mutated, patients frequently present with spastic paraparesis, a thin corpus callosum, and cognitive impairment. We previously delineated a neurodegenerative phenotype in neurons of these patients. In the current study, we recapitulated early developmental phenotypes of SPG11 and outlined their cellular and molecular mechanisms in patient-specific induced pluripotent stem cell (iPSC)-derived cortical neural progenitor cells (NPCs).Methods: We generated and characterized iPSC-derived NPCs and neurons from 3 SPG11 patients and 2 age-matched controls.Results: Gene expression profiling of SPG11-NPCs revealed widespread transcriptional alterations in neurodevelopmental pathways. These include changes in cell-cycle, neurogenesis, cortical development pathways, in addition to autophagic deficits. More important, the GSK3ss-signaling pathway was found to be dysregulated in SPG11-NPCs. Impaired proliferation of SPG11-NPCs resulted in a significant diminution in the number of neural cells. The decrease in mitotically active SPG11-NPCs was rescued by GSK3 modulation.Interpretation: This iPSC-derived NPC model provides the first evidence for an early neurodevelopmental phenotype in SPG11, with GSK3ss as a potential novel target to reverse the disease phenotype.},
author = {Mishra, Himanshu Kumar and Prots, Iryna and Havlicek, Steven and Kohl, Zacharias and Pérez-Brangulí, Francesc and Börstler, Tom and Anneser, Lukas and Minakaki, Georgia and Wend, Holger and Hampl, Martin and Leone, Marina and Brückner, Martina and Klucken, Jochen and Reis, André and Boyer, Leah and Schuierer, Gerhard and Behrens, Jürgen and Lampert, Angelika and Engel, Felix and Gage, Fred H. and Winkler, Jürgen and Winner, Beate},
doi = {10.1002/ana.24633},
faupublication = {yes},
journal = {Annals of Neurology},
pages = {826-840},
peerreviewed = {Yes},
title = {{GSK3ss}-{Dependent} {Dysregulation} of {Neurodevelopment} in {SPG11}-{Patient} {Induced} {Pluripotent} {Stem} {Cell} {Model}},
volume = {79},
year = {2016}
}
@article{faucris.221883787,
abstract = {Background: Although habituation is one of the most ancient and fundamental forms of learning, its regulators and its relevance for human disease are poorly understood. Methods: We manipulated the orthologs of 286 genes implicated in intellectual disability (ID) with or without comorbid autism spectrum disorder (ASD) specifically in Drosophila neurons, and we tested these models in light-off jump habituation. We dissected neuronal substrates underlying the identified habituation deficits and integrated genotype–phenotype annotations, gene ontologies, and interaction networks to determine the clinical features and molecular processes that are associated with habituation deficits. Results: We identified >100 genes required for habituation learning. For 93 of these genes, a role in habituation learning was previously unknown. These genes characterize ID disorders with macrocephaly and/or overgrowth and comorbid ASD. Moreover, individuals with ASD from the Simons Simplex Collection carrying damaging de novo mutations in these genes exhibit increased aberrant behaviors associated with inappropriate, stereotypic speech. At the molecular level, ID genes required for normal habituation are enriched in synaptic function and converge on Ras/mitogen-activated protein kinase (Ras/MAPK) signaling. Both increased Ras/MAPK signaling in gamma-aminobutyric acidergic (GABAergic) neurons and decreased Ras/MAPK signaling in cholinergic neurons specifically inhibit the adaptive habituation response. Conclusions: Our work supports the relevance of habituation learning to ASD, identifies an unprecedented number of novel habituation players, supports an emerging role for inhibitory neurons in habituation, and reveals an opposing, circuit-level-based mechanism for Ras/MAPK signaling. These findings establish habituation as a possible, widely applicable functional readout and target for pharmacologic intervention in ID/ASD.},
author = {Fenckova, Michaela and Blok, Laura E.R. and Asztalos, Lenke and Goodman, David P. and Cizek, Pavel and Singgih, Euginia L. and Glennon, Jeffrey C. and IntHout, Joanna and Zweier, Christiane and Eichler, Evan E. and von Reyn, Catherine R. and Bernier, Raphael A. and Asztalos, Zoltan and Schenck, Annette},
doi = {10.1016/j.biopsych.2019.04.029},
faupublication = {yes},
journal = {Biological Psychiatry},
keywords = {Autism spectrum disorder; Drosophila; GABAergic neurons; Habituation learning; Intellectual disability; Ras/MAPK},
note = {CRIS-Team Scopus Importer:2019-07-09},
peerreviewed = {Yes},
title = {{Habituation} {Learning} {Is} a {Widely} {Affected} {Mechanism} in {Drosophila} {Models} of {Intellectual} {Disability} and {Autism} {Spectrum} {Disorders}},
year = {2019}
}
@article{faucris.123841784,
abstract = {Non-recurrent deletions in 2q24.1, minimally overlapping two genes, NR4A2 and GPD2, were recently described in individuals with language impairment and behavioral and cognitive symptoms. We herewith report on a female patient with a similar phenotype of severe language and mild cognitive impairment, in whom we identified a de novo deletion covering only NR4A2. NR4A2 encodes a transcription factor highly expressed in brain regions critical for speech and language and implicated in dopaminergic neuronal development. Our findings of a de novo deletion of NR4A2 in an individual with mild intellectual disability and prominent speech and language impairment provides further evidence for NR4A2 haploinsufficiency being causative for neurodevelopmental and particularly language phenotypes.},
author = {Reuter, Miriam and Krumbiegel, Mandy and Schlueter, Gregor and Ekici, Arif Bülent and Reis, André and Zweier, Christiane},
doi = {10.1002/ajmg.a.38288},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
note = {EVALuna2:9359},
pages = {2231-2234},
peerreviewed = {Yes},
title = {{Haploinsufficiency} of {NR4A2} is associated with a neurodevelopmental phenotype with prominent language impairment},
volume = {173},
year = {2017}
}
@article{faucris.255362310,
abstract = {Purpose: Proline Rich 12 (PRR12) is a gene of unknown function with suspected DNA-binding activity, expressed in developing mice and human brains. Predicted loss-of-function variants in this gene are extremely rare, indicating high intolerance of haploinsufficiency. Methods: Three individuals with intellectual disability and iris anomalies and truncating de novo PRR12 variants were described previously. We add 21 individuals with similar PRR12 variants identified via matchmaking platforms, bringing the total number to 24. Results: We observed 12 frameshift, 6 nonsense, 1 splice-site, and 2 missense variants and one patient with a gross deletion involving PRR12. Three individuals had additional genetic findings, possibly confounding the phenotype. All patients had developmental impairment. Variable structural eye defects were observed in 12/24 individuals (50%) including anophthalmia, microphthalmia, colobomas, optic nerve and iris abnormalities. Additional common features included hypotonia (61%), heart defects (52%), growth failure (54%), and kidney anomalies (35%). PrediXcan analysis showed that phecodes most strongly associated with reduced predicted PRR12 expression were enriched for eye- (7/30) and kidney- (4/30) phenotypes, such as wet macular degeneration and chronic kidney disease. Conclusion: These findings support PRR12 haploinsufficiency as a cause for a novel disorder with a wide clinical spectrum marked chiefly by neurodevelopmental and eye abnormalities.},
author = {Chowdhury, Fuad and Wang, Lei and Al-Raqad, Mohammed and Amor, David J. and Baxová, Alice and Bendová, Šárka and Biamino, Elisa and Brusco, Alfredo and Caluseriu, Oana and Cox, Nancy J. and Froukh, Tawfiq and Gunay-Aygun, Meral and Hančárová, Miroslava and Haynes, Devon and Heide, Solveig and Hoganson, George and Kaname, Tadashi and Keren, Boris and Kosaki, Kenjiro and Kubota, Kazuo and Lemons, Jennifer M. and Magriña, Maria A. and Mark, Paul R. and McDonald, Marie T. and Montgomery, Sarah and Morley, Gina M. and Ohnishi, Hidenori and Okamoto, Nobuhiko and Rodriguez-Buritica, David and Rump, Patrick and Sedláček, Zdeněk and Schatz, Krista and Streff, Haley and Uehara, Tomoko and Walia, Jagdeep S. and Wheeler, Patricia G. and Wiesener, Antje and Zweier, Christiane and Kawakami, Koichi and Wentzensen, Ingrid M. and Lalani, Seema R. and Siu, Victoria M. and Bi, Weimin and Balci, Tugce B.},
doi = {10.1038/s41436-021-01129-6},
faupublication = {yes},
journal = {Genetics in Medicine},
note = {CRIS-Team Scopus Importer:2021-04-16},
peerreviewed = {Yes},
title = {{Haploinsufficiency} of {PRR12} causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities},
year = {2021}
}
@article{faucris.106290844,
abstract = {Bromodomain PHD finger transcription factor (BPTF) is the largest subunit of nucleosome remodeling factor (NURF), a member of the ISWI chromatin-remodeling complex. However, the clinical consequences of disruption of this complex remain largely uncharacterized. BPTF is required for anterior-posterior axis formation of the mouse embryo and was shown to promote posterior neuroectodermal fate by enhancing Smad2-activated wnt8 expression in zebrafish. Here, we report eight loss-of-function and two missense variants (eight de novo and two of unknown origin) in BPTF on 17q24.2. The BPTF variants were found in unrelated individuals aged between 2.1 and 13 years, who manifest variable degrees of developmental delay/intellectual disability (10/10), speech delay (10/10), postnatal microcephaly (7/9), and dysmorphic features (9/10). Using CRISPR-Cas9 genome editing of bptf in zebrafish to induce a loss of gene function, we observed a significant reduction in head size of F0 mutants compared to control larvae. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and phospho-histone H3 (PH3) staining to assess apoptosis and cell proliferation, respectively, showed a significant increase in cell death in F0 mutants compared to controls. Additionally, we observed a substantial increase of the ceratohyal angle of the craniofacial skeleton in bptf F0 mutants, indicating abnormal craniofacial patterning. Taken together, our data demonstrate the pathogenic role of BPTF haploinsufficiency in syndromic neurodevelopmental anomalies and extend the clinical spectrum of human disorders caused by ablation of chromatin remodeling complexes.},
author = {Stankiewicz, Pawel and Khan, Tahir N. and Szafranski, Przemyslaw and Slattery, Leah and Streff, Haley and Vetrini, Francesco and Bernstein, Jonathan A. and Brown, Chester W. and Rosenfeld, Jill A. and Rednam, Surya and Scollon, Sarah and Bergstrom, Katie L. and Parsons, Donald W. and Plon, Sharon E. and Vieira, Marta W. and Quaio, Caio R. D. C. and Baratela, Wagner A. R. and Acosta Guio, Johanna C. and Armstrong, Ruth and Mehta, Sarju G. and Rump, Patrick and Pfundt, Rolph and Lewandowski, Raymond and Fernandes, Erica M. and Shinde, Deepali N. and Tang, Sha and Hoyer, Juliane and Zweier, Christiane and Reis, André and Bacino, Carlos A. and Xiao, Rui and Breman, Amy M. and Smith, Janice L. and Katsanis, Nicholas and Bostwick, Bret and Popp, Bernt and Davis, Erica E. and Yang, Yaping},
doi = {10.1016/j.ajhg.2017.08.014},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9361},
pages = {503-515},
peerreviewed = {Yes},
title = {{Haploinsufficiency} of the {Chromatin} {Remodeler} {BPTF} {Causes} {Syndromic} {Developmental} and {Speech} {Delay}, {Postnatal} {Microcephaly}, and {Dysmorphic} {Features}},
volume = {101},
year = {2017}
}
@article{faucris.281176954,
abstract = {Purpose: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10. Methods: An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis. Results: We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a broad spectrum of neurodevelopmental disorders and variable congenital anomalies that affect most organ systems and were recapitulated in animal models of altered MYH10 activity. Variants were typically de novo missense changes with clustering observed in the motor domain. MYH10 knockout cells showed defects in primary ciliogenesis and reduced ciliary length with impaired Hedgehog signaling. MYH10 variant overexpression produced a dominant-negative effect on ciliary length. Conclusion: These data presented a novel genetic cause of isolated and syndromic neurodevelopmental disorders related to heterozygous variants in the MYH10 gene with implications for disrupted primary cilia length control and altered Hedgehog signaling in disease pathogenesis.},
author = {Holtz, Alexander M. and Vancoil, Rachel and Vansickle, Elizabeth A. and Carere, Deanna Alexis and Withrow, Kara and Torti, Erin and Juusola, Jane and Millan, Francisca and Person, Richard and Guillen Sacoto, Maria J. and Si, Yue and Wentzensen, Ingrid M. and Pugh, Jada and Vasileiou, Georgia and Rieger, Melissa and Reis, André and Argilli, Emanuela and Sherr, Elliott H. and Aldinger, Kimberly A. and Dobyns, William B. and Brunet, Theresa and Hoefele, Julia and Wagner, Matias and Haber, Benjamin and Kotzaeridou, Urania and Keren, Boris and Heron, Delphine and Mignot, Cyril and Heide, Solveig and Courtin, Thomas and Buratti, Julien and Murugasen, Serini and Donald, Kirsten A. and O'Heir, Emily and Moody, Shade and Kim, Katherine H. and Burton, Barbara K. and Yoon, Grace and Campo, Miguel del and Masser-Frye, Diane and Kozenko, Mariya and Parkinson, Christina and Sell, Susan L. and Gordon, Patricia L. and Prokop, Jeremy W. and Karaa, Amel and Bupp, Caleb and Raby, Benjamin A.},
doi = {10.1016/j.gim.2022.07.005},
faupublication = {yes},
journal = {Genetics in Medicine},
keywords = {Hedgehog signaling; MYH10; Neurodevelopmental disorder; Nonmuscle myosin; Primary cilia},
note = {CRIS-Team Scopus Importer:2022-09-02},
peerreviewed = {Yes},
title = {{Heterozygous} variants in {MYH10} associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in {Hedgehog} signaling},
year = {2022}
}
@article{faucris.122378564,
abstract = {HIBCH (3-hydroxyisobutyryl-CoA hydrolase) deficiency (MIM #250620) is a rare autosomal recessive inborn error of metabolism, leading to a block in the catabolic pathway of the amino acid valine and presumably to accumulation of toxic valine metabolites in mitochondria. Only three families with HIBCH deficiency and biallelic HIBCH mutations have been described. We report on a further patient, first child of healthy consanguineous parents, with severe developmental delay, seizures, hyperintensities of the basal ganglia on magnetic resonance imaging (MRI), progressive brain atrophy, optic nerve atrophy, repeatedly elevated blood lactate, and respiratory chain complexes I, I + III and cytochrome c oxidase deficiencies with borderline depletion of mitochondrial DNA in muscle tissue. Laboratory findings in blood and skeletal muscle were inconsistent and did not allow a definite diagnosis, but supported the hypothesis of mitochondrial dysfunction. Homozygosity mapping and whole-exome sequencing revealed a homozygous one-base pair insertion in HIBCH. Deficiency of enzyme activity was confirmed in cultured fibroblasts. Although relatively unspecific, the clinical features were similar to those of the previously reported cases. Given the clinical variability and large number of differential diagnoses, the prevalence of HIBCH deficiency is probably underestimated. Next-generation sequencing approaches are an effective tool for identifying the underlying genetic basis in patients suspected of mitochondrial disorders. © 2014 Wiley Periodicals, Inc.},
author = {Reuter, Miriam and Sass, Joern Oliver and Leis, Thomas and Koehler, Julia and Mayr, Johannes A. and Feichtinger, Rene G. and Rauh, Manfred and Schanze, Ina and Baehr, Luzy and Trollmann, Regina and Uebe, Steffen and Ekici, Arif Bülent and Reis, André},
doi = {10.1002/ajmg.a.36766},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
note = {EVALuna2:9220},
pages = {3162-9},
peerreviewed = {Yes},
title = {{HIBCH} deficiency in a patient with phenotypic characteristics of mitochondrial disorders},
volume = {164},
year = {2014}
}
@article{faucris.120794784,
abstract = {Infantile Alexander disease is a rare progressive leukodystrophy caused by autosomal dominant mutations in the (GFAP) gene typically presenting with psychomotor retardation, progressive macrocephaly and refractory epilepsy. Neuroradiological hallmarks are extensive white matter lesions with frontal preponderance as well as signal intensity changes of basal ganglia and medulla oblongata with variable contrast enhancement. Here, we report an atypical manifestation in a 21-month-old boy presenting with flaccid paraparesis and areflexia. Cognitive, visual as well as fine motor skills and muscular strength of the upper extremities were appropriate for age. Weight and height as well as head circumference were within normal range. Clinical or electroencephalographic signs of seizures were absent. Cranial MRI demonstrated bifrontal cystic tumorous lesions with partial contrast rims, as well as space-occupying focal lesions of the caudate nuclei. Spinal MRI revealed swelling of the lumbar and cervical spinal cord. CSF and blood chemistry showed normal results. Histopathology of a subcortical lesion showed large amounts of Rosenthal fibers and protein droplets characteristic of Alexander disease. Sequencing detected a heterozygous mutation of the GFAP gene (c.205G > A; p.(Glu69Lys)) that has been reported before as probably pathogenetic in another case of lower spinal involvement. This well documented case draws attention to atypical spinal manifestations of Alexander disease and gives histopathological proof of the pathogenetic role of a rare GFAP mutation with marked spinal involvement.},
author = {Brackmann, Florian and Coras, Roland and Rössler, Karl and Kraus, Cornelia and Rompel, Oliver and Trollmann, Regina},
doi = {10.1016/j.braindev.2017.11.005},
faupublication = {yes},
journal = {Brain & Development},
note = {EVALuna2:9396},
peerreviewed = {Yes},
title = {{Histopathological} proof of the pathogenicity of a rare {GFAP} mutation in a patient with flaccid paraparesis},
year = {2017}
}
@article{faucris.212500805,
abstract = {Although tissue-resident memory T cells (T-RM cells) have been shown to regulate host protection in infectious disorders, their function in inflammatory bowel disease (IBD) remains to be investigated. Here we characterized T-RM cells in human IBD and in experimental models of intestinal inflammation. Pro-inflammatory T-RM cells accumulated in the mucosa of patients with IBD, and the presence of CD4(+)CD69(+)CD103(+) T-RM cells was predictive of the development of flares. In vivo, functional impairment of T-RM cells in mice with double knockout of the T-RM-cell-associated transcription factors Hobit and Blimp-1 attenuated disease in several models of colitis, due to impaired cross-talk between the adaptive and innate immune system. Finally, depletion of T-RM cells led to a suppression of colitis activity. Together, our data demonstrate a central role for T-RM cells in the pathogenesis of chronic intestinal inflammation and suggest that these cells could be targets for future therapeutic approaches in IBD.},
author = {Zundler, Sebastian and Becker, Emily and Spocinska, Marta and Slawik, Monique and Parga-Vidal, Loreto and Stark, Regina and Wiendl, Maximilian and Atreya, Raja and Rath, Timo and Leppkes, Moritz and Hildner, Kai and Lopez Posadas, Rocío and Lukassen, Sören and Ekici, Arif Bülent and Neufert, Clemens and Atreya, Imke and Van Gisbergen, Klaas P. J. M. and Neurath, Markus},
doi = {10.1038/s41590-018-0298-5},
faupublication = {yes},
journal = {Nature Immunology},
note = {CRIS-Team WoS Importer:2019-03-06},
pages = {288-+},
peerreviewed = {Yes},
title = {{Hobit}- and {Blimp}-1-driven {CD4}(+) tissue-resident memory {T} cells control chronic intestinal inflammation},
volume = {20},
year = {2019}
}
@article{faucris.313457842,
abstract = {Studying human somatic cell-to-neuron conversion using primary brain-derived cells as starting cell source is hampered by limitations and variations in human biopsy material. Thus, delineating the molecular variables that allow changing the identity of somatic cells, permit adoption of neuronal phenotypes, and foster maturation of induced neurons (iNs) is challenging. Based on our previous results that pericytes derived from the adult human cerebral cortex can be directly converted into iNs (Karow et al., 2018; Karow et al., 2012), we here introduce human induced pluripotent stem cell (hiPSC)-derived pericytes (hiPSC-pericytes) as a versatile and more uniform tool to study the pericyte-to-neuron conversion process. This strategy enables us to derive scalable cell numbers and allows for engineering of the starting cell population such as introducing reporter tools before differentiation into hiPSC-pericytes and subsequent iN conversion. Harvesting the potential of this approach, we established hiPSC-derived human-human neuronal cocultures that not only allow for independent manipulation of each coculture partner but also resulted in morphologically more mature iNs. In summary, we exploit hiPSC-based methods to facilitate the analysis of human somatic cell-to-neuron conversion.},
author = {Menon, Radhika and Petrucci, Linda and Lohrer, Benjamin and Zhang, Jingzhong and Schulze, Markus and Schichor, Christian and Winner, Beate and Winkler, Jürgen and Riemenschneider, Markus J. and Kühn, Ralf and Falk, Sven and Karow, Marisa},
doi = {10.1089/cell.2023.0008},
faupublication = {yes},
journal = {Cellular Reprogramming},
keywords = {direct lineage reprogramming; induced neurons; organoids; pericytes},
note = {CRIS-Team Scopus Importer:2023-11-03},
pages = {212-223},
peerreviewed = {Yes},
title = {{Human} {Induced} {Pluripotent} {Stem} {Cell}-{Derived} {Pericytes} as {Scalable} and {Editable} {Source} to {Study} {Direct} {Lineage} {Reprogramming} {Into} {Induced} {Neurons}},
volume = {25},
year = {2023}
}
@article{faucris.123485384,
abstract = {While motor neuron diseases are currently incurable, induced pluripotent stem cell research has uncovered some disease-relevant phenotypes. We will discuss strategies to model different aspects of motor neuron disease and the specific neurons involved in the disease. We will then describe recent progress to investigate common forms of motor neuron disease: amyotrophic lateral sclerosis, hereditary spastic paraplegia and spinal muscular atrophy.},
author = {Winner, Beate and Marchetto, Maria C. and Winkler, Jürgen and Gage, Fred H.},
doi = {10.1093/hmg/ddu205},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:25333},
pages = {R27-34},
peerreviewed = {Yes},
title = {{Human}-induced pluripotent stem cells pave the road for a better understanding of motor neuron disease},
volume = {23},
year = {2014}
}
@article{faucris.260537150,
abstract = {In this concise Mini-Review we will summarize ongoing developments of new techniques to study physiology and pathophysiology of the peripheral sensory nervous system in human stem cell derived models. We will focus on recent developments of reprogramming somatic cells into induced pluripotent stem cells, neural differentiation towards neuronal progenitors and human sensory neurons. We will sum up the high potential of this new technique for disease modelling of human neuropathies with a focus on genetic pain syndromes, such as gain- and loss-of-function mutations in voltage-gated sodium channels. The stem cell derived human sensory neurons are used for drug testing and we will summarize their usefulness for individualized treatment identification in patients with neuropathic pain. The review will give an outlook on potential application of this technique as companion diagnostics and for personalized medicine.},
author = {Lampert, Angelika and Bennett, David L. and McDermott, Lucy A. and Neureiter, Anika and Eberhardt, Esther and Winner, Beate and Zenke, Martin},
doi = {10.1016/j.ynpai.2020.100055},
faupublication = {yes},
journal = {Neurobiology of pain (Cambridge, Mass.)},
keywords = {Disease modelling; iPSC; Pain; Peripheral neuron; Stem cell differentiation},
note = {Created from Fastlane, Scopus look-up},
peerreviewed = {Yes},
title = {{Human} sensory neurons derived from pluripotent stem cells for disease modelling and personalized medicine},
volume = {8},
year = {2020}
}
@article{faucris.212982408,
abstract = {SPG11 linked hereditary spastic paraplegia is a complex monogenic neurodegenerative disease that in addition to spastic paraplegia is characterized by childhood onset cognitive impairment, thin corpus callosum and enlarged ventricles. We have previously shown impaired proliferation of SPG11 neural progenitor cells (NPCs). For delineation of potential defect in SPG11 brain development we employ 2D culture systems and 3D human brain organoids derived from SPG11 patients' iPSC and controls. We reveal that an increased rate of asymmetric divisions of neural progenitor cells leads to proliferation defect, causing premature neurogenesis. Correspondingly, SPG11 organoids appeared smaller than controls and had larger ventricles as well as thinner germinal wall. Premature neurogenesis and organoid size were rescued by GSK3-inhibititors including the FDA-approved tideglusib. These findings shed light on the neurodevelopmental mechanisms underlying disease pathology.},
author = {Pérez-Brangulí, Francesc and Buchsbaum, Isabel and Pozner, Tatyana and Regensburger, Martin and Fan, Wenqiang and Schray, Annika and Börstler, Tom and Mishra, Himanshu Kumar and Gräf, Daniela and Kohl, Zacharias and Winkler, Jürgen and Berninger, Benedikt and Cappello, Silvia and Winner, Beate},
doi = {10.1093/hmg/ddy397},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:36370},
peerreviewed = {Yes},
title = {{Human} {SPG11} cerebral organoids reveal cortical neurogenesis impairment},
year = {2018}
}
@article{faucris.106287984,
abstract = {Patients with the Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) have a congenital utero-vaginal cervical aplasia, but normal or hypoplastic adnexa and develop with normal female phenotype. Some reports mostly demonstrated regular steroid hormone levels in small MRKH cohorts including single MRKH patients with hyperandrogenemia and a clinical presentationof hirsutism and acne has also been shown. Genetically a correlation of WNT4 mutations with singular MRKH patients and hyperandrogenemia was noted. This study analyzed the hormone status of 215 MRKH patients by determining the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, 17-OH progesterone, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and prolactin to determine the incidence of hyperandrogenemia and hyperprolactinemia in MRKH patients. Additional calculations and a ratio of free androgen index and biologically active testosterone revealed a hyperandrogenemia rate of 48.3%, hyperprolactinemia of 9.8% and combined hyperandrogenemia and hyperprolactinemia of 4.2% in MRKH patients. The rates of hirsutism, acne and especially polycystic ovary syndrome (PCOS) were in the normal range of the population and showed no correlation with hyperandrogenemia. A weekly hormone assessment over 30 days comparing 5 controls and 7 MRKH patients revealed high androgen and prolactin, but lower LH/FSH and SHBG levels with MRKH patients. The sequencing of WNT4, WNT5A, WNT7A and WNT9B demonstrated no significant mutations correlating with hyperandrogenemia. Taken together, this study shows that over 52% of MRKH patients have hyperandrogenemia without clinical presentation and 14% hyperprolactinemia, which appeals for general hormone assessment and adjustments of MRKH patients.},
author = {Oppelt, Patricia and Mueller, Andreas and Stephan, Liana and Dittrich, Ralf and Lermann, Johannes and Büttner, Christian and Ekici, Arif Bülent and Conzelmann, Gabi and Seeger, Harald and Schoeller, Dorit and Rall, Katharina and Beckmann, Matthias and Strissel, Pamela and Brucker, Sara Y. and Strick, Reiner},
doi = {10.1530/REP-16-0408},
faupublication = {yes},
journal = {Reproduction},
note = {EVALuna2:9378},
pages = {555-563},
peerreviewed = {Yes},
title = {{Hyperandrogenemia} and high prolactin in congenital utero-vaginal aplasia patients},
volume = {153},
year = {2017}
}
@article{faucris.122797664,
abstract = {In two independent consanguineous families each with two children affected by mild intellectual disability and microcephaly, we identified two homozygous missense variants (c.119T>A [p.Met40Lys] and c.92T>A [p.Leu31His]) in TATA-box-binding-protein-associated factor 13 (TAF13). Molecular modeling suggested a pathogenic effect of both variants through disruption of the interaction between TAF13 and TAF11. These two proteins form a histone-like heterodimer that is essential for their recruitment into the general RNA polymerase II transcription factor IID (TFIID) complex. Co-immunoprecipitation in HeLa cells transfected with plasmids encoding TAF11 and TAF13 revealed that both variants indeed impaired formation of the TAF13-TAF11 heterodimer, thus confirming the protein modeling analysis. To further understand the functional role of TAF13, we performed RNA sequencing of neuroblastoma cell lines upon TAF13 knockdown. The transcriptional profile showed significant deregulation of gene expression patterns with an emphasis on genes related to neuronal and skeletal functions and those containing E-box motives in their promoters. Here, we expand the spectrum of TAF-associated phenotypes and highlight the importance of TAF13 in neuronal functions.},
author = {Tawamie, Hasan and Martianov, Igor and Wohlfahrt, Natalie and Buchert, Rebecca and Mengus, Gabrielle and Uebe, Steffen and Janiri, Luigi and Hirsch, Franz Wolfgang and Schumacher, Johannes and Ferrazzi, Fulvia and Sticht, Heinrich and Reis, André and Davidson, Irwin and Colombo, Roberto and Abou Jamral, Rami},
doi = {10.1016/j.ajhg.2017.01.032},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9362},
pages = {555-561},
peerreviewed = {Yes},
title = {{Hypomorphic} {Pathogenic} {Variants} in {TAF13} {Are} {Associated} with {Autosomal}-{Recessive} {Intellectual} {Disability} and {Microcephaly}},
volume = {100},
year = {2017}
}
@article{faucris.118508544,
abstract = {To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.},
author = {Phelan, Catherine M. and Kuchenbaecker, Karoline B. and Tyrer, Jonathan P. and Kar, Siddhartha P. and Lawrenson, Kate and Winham, Stacey J. and Dennis, Joe and Pirie, Ailith and Riggan, Marjorie J. and Chornokur, Ganna and Earp, Madalene A. and Lyra, Paulo C. and Lee, Janet M. and Coetzee, Simon and Beesley, Jonathan and Mcguffog, Lesley and Soucy, Penny and Dicks, Ed and Lee, Andrew and Barrowdale, Daniel and Lecarpentier, Julie and Leslie, Goska and Aalfs, Cora M. and Aben, Katja K. H. and Adams, Marcia and Adlard, Julian and Andrulis, Irene L. and Anton-Culver, Hoda and Antonenkova, Natalia and Aravantinos, Gerasimos and Arnold, Norbert and Arun, Banu K. and Arver, Brita and Azzollini, Jacopo and Balmana, Judith and Banerjee, Susana N. and Barjhoux, Laure and Barkardottir, Rosa B. and Bean, Yukie and Beckmann, Matthias and Beeghly-Fadiel, Alicia and Benitez, Javier and Bermisheva, Marina and Bernardini, Marcus Q. and Birrer, Michael J. and Bjorge, Line and Black, Amanda and Blankstein, Kenneth and Blok, Marinus J. and Bodelon, Clara and Bogdanova, Natalia and Bojesen, Anders and Bonanni, Bernardo and Borg, Ake and Bradbury, Angela R. and Brenton, James D. and Brewer, Carole and Brinton, Louise and Broberg, Per and Brooks-Wilson, Angela and Bruinsma, Fiona and Brunet, Joan and Buecher, Bruno and Butzow, Ralf and Buys, Saundra S. and Caldes, Trinidad and Caligo, Maria A. and Campbell, Ian and Cannioto, Rikki and Carney, Michael E. and Cescon, Terence and Chan, Salina B. and Chang-Claude, Jenny and Chanock, Stephen and Chen, Xiao Qing and Chiew, Yoke-Eng and Chiquette, Jocelyne and Chung, Wendy K. and Claes, Kathleen B. M. and Conner, Thomas and Cook, Linda S. and Cook, Jackie and Cramer, Daniel W. and Cunningham, Julie M. and D'Aloisio, Aimee A. and Daly, Mary B. and Damiola, Francesca and Damirovna, Sakaeva Dina and Dansonka-Mieszkowska, Agnieszka and Dao, Fanny and Davidson, Rosemarie and Defazio, Anna and Delnatte, Capucine and Doheny, Kimberly F. and Diez, Orland and Ding, Yuan Chun and Doherty, Jennifer Anne and Domchek, Susan M. and Dorfling, Cecilia M. and Dork, Thilo and Dossus, Laure and Duran, Mercedes and Durst, Matthias and Dworniczak, Bernd and Eccles, Diana and Edwards, Todd and Eeles, Ros and Eilber, Ursula and Ejlertsen, Bent and Ekici, Arif Bülent and Ellis, Steve and Elvira, Mingajeva and Eng, Kevin H. and Engel, Christoph and Evans, D. Gareth and Fasching, Peter and Ferguson, Sarah and Ferrer, Sandra Fert and Flanagan, James M. and Fogarty, Zachary C. and Fortner, Renee T. and Fostira, Florentia and Foulkes, William D. and Fountzilas, George and Fridley, Brooke L. and Friebel, Tara M. and Friedman, Eitan and Frost, Debra and Ganz, Patricia A. and Garber, Judy and Garcia, Maria J. and Garcia-Barberan, Vanesa and Gehrig, Andrea and Gentry-Maharaj, Aleksandra and Gerdes, Anne-Marie and Giles, Graham G. and Glasspool, Rosalind and Glendon, Gord and Godwin, Andrew K. and Goldgar, David E. and Goranova, Teodora and Gore, Martin and Greene, Mark H. and Gronwald, Jacek and Gruber, Stephen and Hahnen, Eric and Haiman, Christopher A. and Hakansson, Niclas and Hamann, Ute and Hansen, Thomas V. O. and Harrington, Patricia A. and Harris, Holly R. and Hauke, Jan and Hein, Alexander and Henderson, Alex and Hildebrandt, Michelle A. T. and Hillemanns, Peter and Hodgson, Shirley and Hogdall, Claus K. and Hogdall, Estrid and Hogervorst, Frans B. L. and Holland, Helene and Hooning, Maartje J. and Hosking, Karen and Huang, Ruea-Yea and Hulick, Peter J. and Hung, Jillian and Hunter, David J. and Huntsman, David G. and Huzarski, Tomasz and Imyanitov, Evgeny N. and Isaacs, Claudine and Iversen, Edwin S. and Izatt, Louise and Izquierdo, Angel and Jakubowska, Anna and James, Paul and Janavicius, Ramunas and Jernetz, Mats and Jensen, Allan and Jensen, Uffe Birk and John, Esther M. and Johnatty, Sharon and Jones, Michael E. and Kannisto, Paivi and Karlan, Beth Y. and Karnezis, Anthony and Kast, Karin and Kennedy, Catherine J. and Khusnutdinova, Elza and Kiemeney, Lambertus A. and Kiiski, Johanna I. and Kim, Sung-Won and Kjaer, Susanne K. and Kobel, Martin and Kopperud, Reidun K. and Kruse, Torben A. and Kupryjanczyk, Jolanta and Kwong, Ava and Laitman, Yael and Lambrechts, Diether and Larranaga, Nerea and Larson, Melissa C. and Lazaro, Conxi and Le, Nhu D. and Le Marchand, Loic and Lee, Jong Won and Lele, Shashikant B. and Leminen, Arto and Leroux, Dominique and Lester, Jenny and Lesueur, Fabienne and Levine, Douglas A. and Liang, Dong and Liebrich, Clemens and Lilyquist, Jenna and Lipworth, Loren and Lissowska, Jolanta and Lu, Karen H. and Lubinski, Jan and Luccarini, Craig and Lundvall, Lene and Mai, Phuong L. and Mendoza-Fandino, Gustavo and Manoukian, Siranoush and Massuger, Leon F. A. G. and May, Taymaa and Mazoyer, Sylvie and Mcalpine, Jessica N. and Mcguire, Valerie and Mclaughlin, John R. and Mcneish, Iain and Meijers-Heijboer, Hanne and Meindl, Alfons and Menon, Usha and Mensenkamp, Arjen R. and Merritt, Melissa A. and Milne, Roger L. and Mitchell, Gillian and Modugno, Francesmary and Moes-Sosnowska, Joanna and Moffitt, Melissa and Montagna, Marco and Moysich, Kirsten B. and Mulligan, Anna Marie and Musinsky, Jacob and Nathanson, Katherine L. and Nedergaard, Lotte and Ness, Roberta B. and Neuhausen, Susan L. and Nevanlinna, Heli and Niederacher, Dieter and Nussbaum, Robert L. and Odunsi, Kunle and Olah, Edith and Olopade, Olufunmilayo I. and Olsson, Hakan and Olswold, Curtis and O'Malley, David M. and Ong, Kai-Ren and Onland-Moret, N. Charlotte and Orr, Nicholas and Orsulic, Sandra and Osorio, Ana and Palli, Domenico and Papi, Laura and Park-Simon, Tjoung-Won and Paul, James and Pearce, Celeste L. and Pedersen, Inge Sokilde and Peeters, Petra H. M. and Peissel, Bernard and Peixoto, Ana and Pejovic, Tanja and Pelttari, Liisa M. and Permuth, Jennifer B. and Peterlongo, Paolo and Pezzani, Lidia and Pfeiler, Georg and Phillips, Kelly-Anne and Piedmonte, Marion and Pike, Malcolm C. and Piskorz, Anna M. and Poblete, Samantha R. and Pocza, Timea and Poole, Elizabeth M. and Poppe, Bruce and Porteous, Mary E. and Prieur, Fabienne and Prokofyeva, Darya and Pugh, Elizabeth and Pujana, Miquel Angel and Pujol, Pascal and Radice, Paolo and Rantala, Johanna and Rappaport-Fuerhauser, Christine and Rennert, Gad and Rhiem, Kerstin and Rice, Patricia and Richardson, Andrea and Robson, Mark and Rodriguez, Gustavo C. and Rodriguez-Antona, Cristina and Romm, Jane and Rookus, Matti A. and Rossing, Mary Anne and Rothstein, Joseph H. and Rudolph, Anja and Runnebaum, Ingo B. and Salvesen, Helga B. and Sandler, Dale P. and Schoemaker, Minouk J. and Senter, Leigha and Setiawan, V. Wendy and Severi, Gianluca and Sharma, Priyanka and Shelford, Tameka and Siddiqui, Nadeem and Side, Lucy E. and Sieh, Weiva and Singer, Christian F. and Sobol, Hagay and Song, Honglin and Southey, Melissa C. and Spurdle, Amanda B. and Stadler, Zsofia and Steinemann, Doris and Stoppa-Lyonnet, Dominique and Sucheston-Campbell, Lara E. and Sukiennicki, Grzegorz and Sutphen, Rebecca and Sutter, Christian and Swerdlow, Anthony J. and Szabo, Csilla I. and Szafron, Lukasz and Tan, Yen Y. and Taylor, Jack A. and Tea, Muy-Kheng and Teixeira, Manuel R. and Teo, Soo-Hwang and Terry, Kathryn L. and Thompson, Pamela J. and Thomsen, Liv Cecilie Vestrheim and Thull, Darcy L. and Tihomirova, Laima and Tinker, Anna V. and Tischkowitz, Marc and Tognazzo, Silvia and Toland, Amanda Ewart and Tone, Alicia and Trabert, Britton and Travis, Ruth C. and Trichopoulou, Antonia and Tung, Nadine and Tworoger, Shelley S. and Van Altena, Anne M. and Van Den Berg, David and Van Der Hout, Annemarie H. and Van Der Luijt, Rob B. and Van Heetvelde, Mattias and Van Nieuwenhuysen, Els and Van Rensburg, Elizabeth J. and Vanderstichele, Adriaan and Varon-Mateeva, Raymonda and Vega, Ana and Edwards, Digna Velez and Vergote, Ignace and Vierkant, Robert A. and Vijai, Joseph and Vratimos, Athanassios and Walker, Lisa and Walsh, Christine and Wand, Dorothea and Wang-Gohrke, Shan and Wappenschmidt, Barbara and Webb, Penelope M. and Weinberg, Clarice R. and Weitzel, Jeffrey N. and Wentzensen, Nicolas and Whittemore, Alice S. and Wijnen, Juul T. and Wilkens, Lynne R. and Wolk, Alicja and Woo, Michelle and Wu, Xifeng and Wu, Anna H. and Yang, Hannah and Yannoukakos, Drakoulis and Ziogas, Argyrios and Zorn, Kristin K. and Narod, Steven A. and Easton, Douglas F. and Amos, Christopher I. and Schildkraut, Joellen M. and Ramus, Susan J. and Ottini, Laura and Goodman, Marc T. and Park, Sue K. and Kelemen, Linda E. and Risch, Harvey A. and Thomassen, Mads and Offit, Kenneth and Simard, Jacques and Schmutzler, Rita Katharina and Hazelett, Dennis and Monteiro, Alvaro N. and Couch, Fergus J. and Berchuck, Andrew and Chenevix-Trench, Georgia and Goode, Ellen L. and Sellers, Thomas A. and Gayther, Simon A. and Antoniou, Antonis C. and Pharoah, Paul D. P.},
doi = {10.1038/ng.3826},
faupublication = {yes},
journal = {Nature Genetics},
note = {EVALuna2:9375},
pages = {680-691},
peerreviewed = {Yes},
title = {{Identification} of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer},
volume = {49},
year = {2017}
}
@article{faucris.205193887,
abstract = {Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
},
author = {O'Mara, Tracy A. and Glubb, Dylan M. and Amant, Frederic and Annibali, Daniela and Ashton, Katie and Attia, John and Auer, Paul L. and Beckmann, Matthias and Black, Amanda and Bolla, Manjeet K. and Brauch, Hiltrud and Brenner, Hermann and Brinton, Louise and Buchanan, Daniel D. and Burwinkel, Barbara and Chang-Claude, Jenny and Chanock, Stephen J. and Chen, Chu and Chen, Maxine M. and Cheng, Timothy H. T. and Clarke, Christine L. and Clendenning, Mark and Cook, Linda S. and Couch, Fergus J. and Cox, Angela and Crous-Bous, Marta and Czene, Kamila and Day, Felix and Dennis, Joe and Depreeuw, Jeroen and Doherty, Jennifer Anne and Dork, Thilo and Dowdy, Sean C. and Duerst, Matthias and Ekici, Arif Bülent and Fasching, Peter and Fridley, Brooke L. and Friedenreich, Christine M. and Fritschi, Lin and Fung, Jenny and Garcia-Closas, Montserrat and Gaudet, Mia M. and Giles, Graham G. and Goode, Ellen L. and Gorman, Maggie and Haiman, Christopher A. and Hall, Per and Hankison, Susan E. and Healey, Catherine S. and Hein, Alexander and Hillemanns, Peter and Hodgson, Shirley and Hoivik, Erling A. and Holliday, Elizabeth G. and Hopper, John L. and Hunter, David J. and Jones, Angela and Krakstad, Camilla and Kristensen, Vessela N. and Lambrechts, Diether and Le Marchand, Loic and Liang, Xiaolin and Lindblom, Annika and Lissowska, Jolanta and Long, Jirong and Lu, Lingeng and Magliocco, Anthony M. and Martin, Lynn and Mcevoy, Mark and Meindl, Alfons and Michailidou, Kyriaki and Milne, Roger L. and Mints, Miriam and Montgomery, Grant W. and Nassir, Rami and Olsson, Haekan and Orlow, Irene and Otton, Geoffrey and Palles, Claire and Perry, John R. B. and Peto, Julian and Pooler, Loreall and Prescott, Jennifer and Proietto, Tony and Rebbeck, Timothy R. and Risch, Harvey A. and Rogers, Peter A. W. and Rübner, Matthias and Runnebaum, Ingo and Sacerdote, Carlotta and Sarto, Gloria E. and Schumacher, Fredrick and Scott, Rodney J. and Setiawan, V. Wendy and Shah, Mitul and Sheng, Xin and Shu, Xiao-Ou and Southey, Melissa C. and Swerdlow, Anthony J. and Tham, Emma and Trovik, Jone and Turman, Constance and Tyrer, Jonathan P. and Vachon, Celine and Vanden Berg, David and Vanderstichele, Adriaan and Wang, Zhaoming and Webb, Penelope M. and Wentzensen, Nicolas and Werner, Henrica M. J. and Winham, Stacey J. and Wolk, Alicja and Xia, Lucy and Xiang, Yong-Bing and Yang, Hannah P. and Yu, Herbert and Zheng, Wei and Pharoah, Paul D. P. and Dunning, Alison M. and Kraft, Peter and De Vivo, Immaculata and Tomlinson, Ian and Easton, Douglas F. and Spurdle, Amanda B. and Thompson, Deborah J.},
doi = {10.1038/s41467-018-05427-7},
faupublication = {yes},
journal = {Nature Communications},
note = {EVALuna2:34618},
peerreviewed = {Yes},
title = {{Identification} of nine new susceptibility loci for endometrial cancer},
volume = {9},
year = {2018}
}
@inproceedings{faucris.228303019,
address = {LONDON},
author = {Thiel, Christian and Hauer, Nadine and Vogl, C. and Ahmadian, R. and Dhandapany, P. S. and Popp, Bernt and Buettner, C. and Ube, S. and Sticht, Heinrich and Ferrazzi, Fulvia and Ekici, Arif Bülent and De Luca, A. and Schoeller, E. and Schuhmann, Sarah and Heath, K. E. and Hisado-Oliva, A. and Klinger, Patricia and Boppudi, S. and Kelkel, J. and Jung, A. M. and Kraus, Cornelia and Trautmann, Udo and Wiesener, A. and Kutsche, K. and Rauch, A. and Wieczorek, D. and Rohrer, T. and Zenker, M. and Dörr, Helmuth-Günther and Wiesmann da Silva Reis, André},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2018-06-16/2018-06-19},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {128-128},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{Identification} of novel candidate genes for idiopathic short stature using whole exome sequencing},
venue = {Milan, ITALY},
year = {2019}
}
@inproceedings{faucris.248095044,
address = {LONDON},
author = {Vogl, C. and Keßler, Kristin and Gießl, Andreas and Kirchner, P. and Büttner, Christian and Ekici, Arif Bülent and Reis, André and Thiel, C. T.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {253-253},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Identification} of the deregulated {NEK1} protein network in skeletal ciliopathies},
year = {2020}
}
@article{faucris.280836389,
abstract = {Purpose: To identify molecular predictors of grade 3/4 neutropenic or leukopenic events (NLE) after chemotherapy using a genome-wide association study (GWAS). Experimental Design: A GWAS was performed on patients in the phase III chemotherapy study SUCCESS-A (n = 3,322). Genotyping was done using the Illumina HumanOmniExpress-12v1 array. Findings were functionally validated with cell culture models and the genotypes and gene expression of possible causative genes were correlated with clinical treatment response and prognostic outcomes. Results: One locus on chromosome 16 (rs4784750; NLRC5; P = 1.56E-8) and another locus on chromosome 13 (rs16972207; TNFSF13B; P = 3.42E-8) were identified at a genome-wide significance level. Functional validation revealed that expression of these two genes is altered by genotype-dependent and chemotherapy-dependent activity of two transcription factors. Genotypes also showed an association with disease-free survival in patients with an NLE. Conclusions: Two loci in NLRC5 and TNFSF13B are associated with NLEs. The involvement of theMHCI regulator NLRC5 implies the possible involvement of immuno-oncological pathways.},
author = {Fasching, Peter and Liu, Duan and Scully, Steve and Ingle, James N. and Lyra, Paulo C. and Rack, Brigitte and Hein, Alexander and Ekici, Arif Bülent and Reis, André and Schneeweiss, Andreas and Tesch, Hans and Fehm, Tanja N. and Heinrich, Georg and Beckmann, Matthias and Rübner, Matthias and Hübner, Hanna and Lambrechts, Diether and Madden, Ebony and Shen, Jess and Romm, Jane and Doheny, Kim and Jenkins, Gregory D. and Carlson, Erin E. and Li, Liang and Fridley, Brooke L. and Cunningham, Julie M. and Janni, Wolfgang and Monteiro, Alvaro N.A. and Schaid, Daniel J. and Häberle, Lothar and Weinshilboum, Richard M. and Wang, Liewei},
doi = {10.1158/1078-0432.CCR-20-4774},
faupublication = {yes},
journal = {Clinical Cancer Research},
note = {CRIS-Team Scopus Importer:2022-08-19},
pages = {3342-3355},
peerreviewed = {Yes},
title = {{Identification} of {Two} {Genetic} {Loci} {Associated} with {Leukopenia} after {Chemotherapy} in {Patients} with {Breast} {Cancer}},
volume = {28},
year = {2022}
}
@article{faucris.109213984,
abstract = {We analysed the influence of rhinovirus (RV) in nasopharyngeal fluid (NPF) on type I and III interferon (IFN) responses (e.g. IFN-? and IFN -: ?) and their signal transduction, at baseline and during disease exacerbation, in cohorts of pre-school children with and without asthma.At the time of recruitment into the Europe-wide study PreDicta, and during symptoms, NPF was collected and the local RV colonisation was analysed. Peripheral blood mononuclear cells (PBMCs) were challenged in vitro with RV or not. RNA was analysed by quantitative real-time PCR and gene arrays. Serum was analysed with ELISA for IFNs and C-reactive protein.We found that PBMCs from asthmatic children infected in vitro with the RV1b serotype upregulated MYD88, IRF1, STAT1 and STAT2 mRNA, whereas MYD88, IRF1, STAT1 and IRF9 were predominantly induced in control children. Moreover, during symptomatic visits because of disease exacerbation associated with RV detection in NPF, IFN-? production was found increased, while IFN-? secretion was already induced by RV in asthmatic children at baseline.During asthma exacerbations associated with RV, asthmatic children can induce IFN-? secretion, indicating a hyperactive immune response to repeated respiratory virus infection.},
author = {Bergauer, Annika and Sopel, Nina and Kross, Bettina and Vuorinen, Tytti and Xepapadaki, Paraskevi and Weiss, Scott T. and Blau, Ashley and Sharma, Himanshu and Kraus, Cornelia and Springel, Rebekka and Rauh, Manfred and Mittler, Susanne and Graser, Anna and Zimmermann, Theodor and Melichar, Volker O. and Kiefer, Alexander and Kowalski, Marek L. and Sobanska, Anna and Jartti, Tuomas and Lukkarinen, Heikki and Papadopoulos, Nikolaos G. and Finotto, Susetta},
doi = {10.1183/13993003.00969-2016},
faupublication = {yes},
journal = {European Respiratory Journal},
note = {EVALuna2:9365},
peerreviewed = {Yes},
title = {{IFN}-α/{IFN}-λ responses to respiratory viruses in paediatric asthma},
year = {2016}
}
@article{faucris.110673024,
author = {Bergauer, Annika and Sopel, Nina and Kross, Bettina and Vuorinen, Tytti and Xepapadaki, Paraskevi and Weiss, Scott T. and Blau, Ashley and Sharma, Himanshu and Kraus, Cornelia and Springel, Rebekka and Rauh, Manfred and Mittler, Susanne and Graser, Anna and Zimmermann, Theodor and Melichar, Volker O. and Kiefer, Alexander and Kowalski, Marek L. and Sobanska, Anna and Jartti, Tuomas and Lukkarinen, Heikki and Papadopoulos, Nikolaos G. and Finotto, Susetta},
doi = {10.1183/13993003.00006-2017},
faupublication = {yes},
journal = {European Respiratory Journal},
note = {EVALuna:34061},
peerreviewed = {Yes},
title = {{IFN}-α/{IFN}-λ responses to respiratory viruses in paediatric asthma},
volume = {49},
year = {2017}
}
@article{faucris.109514724,
abstract = {Recently, a novel subset of TCR??(+) CD4(-) CD8(-) double-negative (DN) T cells was described to suppress immune responses in both mice and humans. Moreover, in murine models, infusion and/or activation of DN T cells specifically suppressed alloreactive T cells and prevented the development of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. We demonstrated that human DN T cells, like their murine counterparts, are highly potent suppressor cells of both CD4(+) and CD8(+) T cell responses. After hematopoietic stem cell transplantation and other lymphopenic conditions, IL-7 plays an important role in the reconstitution, survival, and homeostasis of the T cell compartment. Because IL-7 was shown to interfere with T cell functionality, we asked whether IL-7 affects the functionality of human DN T cells. Intriguingly, IL-7 diminished the suppressive activity of DN T cells toward allogeneic CD4(+) effector T cells. Of interest, our studies revealed that IL-7 activates the Akt/mechanistic target of rapamycin (mTOR) pathway in human DN T cells. Importantly, selective inhibition of the protein kinases Akt or mTOR reversed the IL-7 effect, thereby restoring the functionality of DN T cells, whereas inhibition of other central T cell signaling pathways did not. Further analyses suggest that the IL-7/Akt/mTOR signaling cascade downregulates anergy-associated genes and upregulates activation- and proliferation-associated factors that may be crucial for DN T cell functionality. These findings indicate that IL-7 and Akt/mTOR signaling are critical factors for the suppressive capacity of DN T cells. Targeting of these pathways by pharmacological agents may restore and/or enhance DN T cell functionality in graft-versus-host disease.},
author = {Allgäuer, Andrea and Schreiner, Elisabeth and Ferrazzi, Fulvia and Ekici, Arif Bülent and Gerbitz, Armin and Mackensen, Andreas and Voelkl, Simon},
doi = {10.4049/jimmunol.1501389},
faupublication = {yes},
journal = {Journal of Immunology},
note = {EVALuna2:9259},
pages = {3139-48},
peerreviewed = {Yes},
title = {{IL}-7 {Abrogates} the {Immunosuppressive} {Function} of {Human} {Double}-{Negative} {T} {Cells} by {Activating} {Akt}/{mTOR} {Signaling}},
volume = {195},
year = {2015}
}
@inproceedings{faucris.222111490,
address = {LONDON},
author = {Assmann, Gunter and Bittenbring, Joerg Thomas and Wagner, Annette D. and Schreiber, Martin and Christofyllakis, Konstantinos and Hüffmeier, Ulrike and Pfoehler, Claudia and Neumann, Frank},
booktitle = {ANNALS OF THE RHEUMATIC DISEASES},
date = {2019-06-12/2019-06-15},
doi = {10.1136/annrheumdis-2019-eular.4145},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-07-12},
pages = {875-876},
peerreviewed = {unknown},
publisher = {BMJ PUBLISHING GROUP},
title = {{IMPACT} {OF} {INTERLEUKIN} 17 {BLOCKING} {AGENT} {ON} {CLINICAL} {OUTCOME} {IN} {SAPHO} {PATIENTS}},
venue = {Madrid},
year = {2019}
}
@article{faucris.313458337,
abstract = {The gut microbiome plays a pivotal role in maintaining human health, with numerous studies demonstrating that alterations in microbial compositions can significantly affect the development and progression of various immune-mediated diseases affecting both the digestive tract and the central nervous system (CNS). This complex interplay between the microbiota, the gut, and the CNS is referred to as the gut–brain axis. The role of the gut microbiota in the pathogenesis of neurodegenerative diseases has gained increasing attention in recent years, and evidence suggests that gut dysbiosis may contribute to disease development and progression. Clinical studies have shown alterations in the composition of the gut microbiota in multiple sclerosis patients, with a decrease in beneficial bacteria and an increase in pro-inflammatory bacteria. Furthermore, changes within the microbial community have been linked to the pathogenesis of Parkinson’s disease and Alzheimer’s disease. Microbiota–gut–brain communication can impact neurodegenerative diseases through various mechanisms, including the regulation of immune function, the production of microbial metabolites, as well as modulation of host-derived soluble factors. This review describes the current literature on the gut–brain axis and highlights novel communication systems that allow cross-talk between the gut microbiota and the host that might influence the pathogenesis of neuroinflammation and neurodegeneration.},
author = {Stolzer, Iris and Scherer, Eveline and Süß, Patrick and Rothhammer, Veit and Winner, Beate and Neurath, Markus and Günther, Claudia},
doi = {10.3390/ijms241914925},
faupublication = {yes},
journal = {International Journal of Molecular Sciences},
keywords = {gut–brain-axis; microbial dysbiosis; neurodegenerative diseases},
note = {CRIS-Team Scopus Importer:2023-11-03},
peerreviewed = {Yes},
title = {{Impact} of {Microbiome}–{Brain} {Communication} on {Neuroinflammation} and {Neurodegeneration}},
volume = {24},
year = {2023}
}
@article{faucris.205203163,
abstract = {PURPOSE: The voice is the most important instrument of communication. Tissue defects in the vocal fold (VF) area lead to serious reduction in quality of life, but thus far, no satisfactory VF implant exists. Therefore, we aim to establish a functional VF implant in a rabbit model by magnetic tissue engineering (MTE) using superparamagnetic iron oxide nanoparticles (SPION). Hence, iron quantification over time as well as cell behavior studies upon SPION treatment are of great importance.
METHODS: Rabbit VF fibroblasts (VFF) were treated with different concentrations of SPIONs (20, 40, and 80 μg/cm2), and iron content was examined for up to 40 days using microwave plasma-atom emission spectroscopy. The effects of SPION treatment on VFF (adhesion, spreading, and migration), which are important for the formation of 3D structures, were tested.
RESULTS: Cellular SPION quantification revealed that there was no residual iron remaining in VFFs after 40 days. SPIONs had a dose-dependent effect on cell adhesion, with good tolerability observed up to 20 μg/cm2. Migration and spreading were not significantly influenced by SPION treatment up to 80 μg/cm2.
DISCUSSION AND CONCLUSION: To develop 3D structures, cell behavior should not be affected by SPION uptake. After 40 days, cells were free of iron as a result of metabolism or rarefication during cell division. Cell functions including adhesion, spreading, and migration were proven to be intact in a dose-dependent manner after SPION treatment, suggesting a safe usage of MTE for voice rehabilitation. Our results thus constitute a solid basis for a successful transfer of this technique into 3D constructs, in order to provide an individual and personalized human VF implant in the future.},
author = {Poettler, Marina and Fliedner, Anna and Schreiber, Eveline and Janko, Christina and Friedrich, Ralf P. and Bohr, Christopher and Döllinger, Michael and Alexiou, Christoph and Dürr, Stephan},
doi = {10.1186/s11671-017-2045-5},
faupublication = {yes},
journal = {Nanoscale Research Letters},
note = {EVALuna2:33203},
peerreviewed = {Yes},
title = {{Impact} of {Superparamagnetic} {Iron} {Oxide} {Nanoparticles} on {Vocal} {Fold} {Fibroblasts}: {Cell} {Behavior} and {Cellular} {Iron} {Kinetics}},
volume = {12},
year = {2017}
}
@article{faucris.205627624,
abstract = {Swiprosin-1/Efhd2 (Efhd2) is highly expressed in the CNS during development and in the adult. EFHD2 is regulated by Ca2+ binding, stabilizes F-actin, and promotes neurite extension. Previous studies indicated a dysregulation of EFHD2 in human Alzheimer's disease brains. We hypothesized a detrimental effect of genetic ablation of Efhd2 on hippocampal integrity and specifically investigated adult hippocampal neurogenesis. Efhd2 was expressed throughout adult neuronal development and in mature neurons. We observed a severe reduction of the survival of adult newborn neurons in Efhd2 knockouts, starting at the early neuroblast stage. Spine formation and dendrite growth of newborn neurons were compromised in full Efhd2 knockouts, but not upon cell-autonomous Efhd2 deletion. Together with our finding of severe hippocampal tauopathy in Efhd2 knockout mice, these data connect Efhd2 to impaired synaptic plasticity as present in Alzheimer's disease and identify a role of Efhd2 in neuronal survival and synaptic integration in the adult hippocampus.},
author = {Regensburger, Martin and Prots, Iryna and Reimer, Dorothea and Brachs, Sebastian and Loskarn, Sandra and Lie, Dieter Chichung and Mielenz, Dirk and Winner, Beate},
doi = {10.1016/j.stemcr.2017.12.010},
faupublication = {yes},
journal = {Stem Cell Reports},
note = {EVALuna2:34019},
pages = {347-355},
peerreviewed = {Yes},
title = {{Impact} of {Swiprosin}-1/{Efhd2} on {Adult} {Hippocampal} {Neurogenesis}},
volume = {10},
year = {2018}
}
@article{faucris.291583134,
abstract = {Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While most of the current treatment strategies focus on immune cell regulation, except for the drug siponimod, there is no therapeutic intervention that primarily aims at neuroprotection and remyelination. Recently, nimodipine showed a beneficial and remyelinating effect in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Nimodipine also positively affected astrocytes, neurons, and mature oligodendrocytes. Here we investigated the effects of nimodipine, an L-type voltage-gated calcium channel antagonist, on the expression profile of myelin genes and proteins in the oligodendrocyte precursor cell (OPC) line Oli-Neu and in primary OPCs. Our data indicate that nimodipine does not have any effect on myelin-related gene and protein expression. Furthermore, nimodipine treatment did not result in any morphological changes in these cells. However, RNA sequencing and bioinformatic analyses identified potential micro (mi)RNA that could support myelination after nimodipine treatment compared to a dimethyl sulfoxide (DMSO) control. Additionally, we treated zebrafish with nimodipine and observed a significant increase in the number of mature oligodendrocytes (* p≤ 0.05). Taken together, nimodipine seems to have different positive effects on OPCs and mature oligodendrocytes.},
author = {Enders, Michael and Weier, Alicia and Chunder, Rittika and An, Young and Bremm, Franziska and Feigenspan, Andreas and Büttner, Christian and Ekici, Arif Bülent and Mingardo, Enrico and Odermatt, Benjamin and Kuerten, Stefanie},
doi = {10.3390/ijms24043716},
faupublication = {yes},
journal = {International Journal of Molecular Sciences},
keywords = {dihydropyridines; MS; myelination; neuroprotection; nimodipine; Oli-Neu; OPC; zebrafish},
note = {CRIS-Team Scopus Importer:2023-03-10},
peerreviewed = {Yes},
title = {{Impact} of the {Voltage}-{Gated} {Calcium} {Channel} {Antagonist} {Nimodipine} on the {Development} of {Oligodendrocyte} {Precursor} {Cells}},
volume = {24},
year = {2023}
}
@article{faucris.308579199,
abstract = {Epigenetic remodeling is emerging as a critical process for several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Genetics alone fails to explain the etiology of ALS, the investigation of the epigenome might therefore provide novel insights into the molecular mechanisms of the disease. In this study, we interrogated the epigenetic landscape in peripheral blood mononuclear cells (PBMCs) of familial ALS (fALS) patients with either chromosome 9 open reading frame 72 (C9orf72) or superoxide dismutase 1 (SOD1) mutation and aimed to identify key epigenetic footprints of the disease. To this end, we used an integrative approach that combines chromatin immunoprecipitation targeting H3K27me3 (ChIP-Seq) with the matching gene expression data to gain new insights into the likely impact of blood-specific chromatin remodeling on ALS-related molecular mechanisms. We demonstrated that one of the hub molecules that modulates changes in PBMC transcriptome in SOD1-mutant ALS patients is ATF3, which has been previously reported in an SOD1 G93A mouse model. We also identified potential suppression of SNAP25, with impaired ATF3 signaling in SOD1-mutant ALS blood. Together, our study shed light on the mechanistic underpinnings of SOD1 mutations in ALS.},
author = {Yazar, Volkan and Kühlwein, Julia K. and Knehr, Antje and Grozdanov, Veselin and Ekici, Arif Bülent and Ludolph, Albert C. and Danzer, Karin M.},
doi = {10.1038/s41598-023-38684-8},
faupublication = {yes},
journal = {Scientific Reports},
note = {CRIS-Team Scopus Importer:2023-08-04},
peerreviewed = {Yes},
title = {{Impaired} {ATF3} signaling involves {SNAP25} in {SOD1} mutant {ALS} patients},
volume = {13},
year = {2023}
}
@article{faucris.205194349,
abstract = {Synucleinopathies including Parkinson's disease (PD) are characterized by the accumulation of alpha-synuclein (?-syn) within neural cell bodies and their processes. Transgenic mice overexpressing human wild-type or mutant forms of ?-syn under the control of different promoters were developed to analyse the underlying neuropathology of PD. One of the earliest clinical symptoms associated with PD is olfactory impairment. The generation of new neurons persists up to adulthood in mammals, in particular the olfactory bulb (OB). In order to assess this process in relation to ?-syn accumulation, we used mice overexpressing human wild-type ?-syn under the regulatable control (tet-off) of the calcium/calmodulin-dependent protein kinase II?-promoter (CaMKII). We observed a decrease in OB neurogenesis in transgenic animals compared to controls using 5-bromo-2'-deoxyuridine (BrdU) to label newly generated cells (neuron-specific nuclear protein; NeuN). After cessation of transgene expression we detected an increase in newly generated cells both in granular (GCL) and glomerular (GLOM) layers of the OB. This led to a rescue of newly generated neurons (BrdU(+)/NeuN(+)) within the GLOM with a distinct specificity for the dopaminergic subpopulation. In contrast, we did not detect a cell-specific rescue of neuronal cells in the GCL suggesting diverse effects of alpha-synucleinopathy in both interneuronal layers of the OB. Colabelling of BrdU with glial markers showed that a differentiation into neither astroglia nor microglia attributed to the observed phenotype in the GCL. In particular, BrdU(+) particles located within microglial cells were predominantly associated close to the membrane therefore the resembling phagocytosed nuclear fragments of BrdU(+) cells. Thus, our study further contributes insights into ?-syn accumulation as a causative player in the impairment of adult neurogenesis and emphasizes its diverse role in cell renewal of distinct OB cell layers.},
author = {May, Verena Elisabeth Luise and Nuber, S. and Marxreiter, Franz and Riess, O. and Winner, Beate and Winkler, Jürgen},
doi = {10.1016/j.neuroscience.2012.07.001},
faupublication = {yes},
journal = {Neuroscience},
note = {EVALuna2:22048},
pages = {343-55},
peerreviewed = {Yes},
title = {{Impaired} olfactory bulb neurogenesis depends on the presence of human wild-type alpha-synuclein},
volume = {222},
year = {2012}
}
@article{faucris.285706724,
abstract = {BackgroundHeterozygous disruptions of FOXP2 were the first identified molecular cause for severe speech disorder: childhood apraxia of speech (CAS), and yet few cases have been reported, limiting knowledge of the condition. MethodsHere we phenotyped 28 individuals from 17 families with pathogenic FOXP2-only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years). Health and development (cognitive, motor, social domains) were examined, including speech and language outcomes with the first cross-linguistic analysis of English and German. ResultsSpeech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%), with similar speech presentations across English and German. Speech was still impaired in adulthood, and some speech sounds (eg, 'th', 'r', 'ch', 'j') were never acquired. Language impairments (21/25, 84%) ranged from mild to severe. Comorbidities included feeding difficulties in infancy (10/27, 37%), fine (13/26, 50%) and gross (13/26, 50%) motor impairment, anxiety (5/27, 19%), depression (6/27, 22%) and sleep disturbance (11/15, 44%). Physical features were common (22/27, 81%) but with no consistent pattern. Cognition ranged from average to mildly impaired and was incongruent with language ability; for example, seven participants with severe language disorder had average non-verbal cognition. ConclusionsAlthough we identify an increased prevalence of conditions like anxiety, depression and sleep disturbance, we confirm that the consequences of FOXP2 dysfunction remain relatively specific to speech disorder, as compared with other recently identified monogenic conditions associated with CAS. Thus, our findings reinforce that FOXP2 provides a valuable entry point for examining the neurobiological bases of speech disorder.},
author = {Morison, Lottie D. and Meffert, Elisabeth and Stampfer, Miriam and Steiner-Wilke, Irene and Vollmer, Brigitte and Schulze, Katrin and Briggs, Tracy and Braden, Ruth and Vogel, Adam and Thompson-Lake, Daisy and Patel, Chirag and Blair, Edward and Goel, Himanshu and Turner, Samantha and Moog, Ute and Riess, Angelika and Liegeois, Frederique and Koolen, David A. and Amor, David J. and Kleefstra, Tjitske and Fisher, Simon E. and Zweier, Christiane and Morgan, Angela T.},
doi = {10.1136/jmg-2022-108734},
faupublication = {yes},
journal = {Journal of Medical Genetics},
note = {CRIS-Team WoS Importer:2022-11-25},
peerreviewed = {Yes},
title = {{In}-depth characterisation of a cohort of individuals with missense and loss-of-function variants disrupting {FOXP2}},
year = {2022}
}
@article{faucris.214176929,
abstract = {Introduction and aims. We aimed to explore the impact of infection diagnosed upon admission and of other clinical baseline parameters on mortality of cirrhotic patients with emergency admissions. Material and methods. We performed a prospective observational monocentric study in a tertiary care center. The association of clinical parameters and established scoring systems with short-term mortality up to 90 days was assessed by univariate and multivariable Cox regression analysis. Akaike's Information Criterion (AIC) was used for automated variable selection. Statistical interaction effects with infection were also taken into account. Results. 218 patients were included. 71.2% were male, mean age was 61.1 +/- 10.5 years. Mean MELD score was 16.2 +/- 6.5, CLIF-consortium Acute on Chronic Liver Failure-score was 34 +/- 11. At 28, 90 and 365 days, 9.6%, 26.0% and 40.6% of patients had died, respectively. In multivariable analysis, respiratory organ failure [Hazard Ratio (HR) = 0.15], albumin substitution (HR = 2.48), non-HCC-malignancy (HR = 4.93), CLIF-C-ACLF (HR = 1.10), HCC (HR = 3.70) and first episode of ascites (HR = 0.11) were significantly associated with 90-day mortality. Patients with infection had a significantly higher 90-day mortality (36.3 vs. 20.1%, p = 0.007). Cultures were positive in 32 patients with resistance to cephalosporins or quinolones in 10, to ampicillin/sulbactam in 14 and carbapenems in 6 patients. Conclusion. Infection is common in cirrhotic ED admissions and increases mortality. The proportion of resistant microorganisms is high. The predictive capacity of established scoring systems in this setting was low to moderate.},
author = {Safi, Wajima and Elnegouly, Mayada and Schellnegger, Raphael and Umgelter, Katrin and Geisler, Fabian and Reindl, Wolfgang and Saugel, Bernd and Hapfelmeier, Alexander and Umgelter, Andreas},
doi = {10.5604/01.3001.0012.2230},
faupublication = {yes},
journal = {Annals of Hepatology},
note = {CRIS-Team WoS Importer:2019-03-22},
pages = {948-958},
peerreviewed = {Yes},
title = {{Infection} and {Predictors} of {Outcome} of {Cirrhotic} {Patients} after {Emergency} {Care} {Hospital} {Admission}},
volume = {17},
year = {2018}
}
@article{faucris.122850904,
abstract = {Synucleinopathies comprise a group of neurodegenerative diseases associated with abnormal accumulation of ?-synuclein. One of the key factors that contribute to the progression of synucleinopathies is neuroinflammation. However, the role of lymphocytes in synucleinopathies like Parkinson's disease (PD) remains largely unclear.To investigate how lymphocytes impact synucleinopathies, human wild-type ?-synuclein (WTS) transgenic mice were crossed with mice lacking mature lymphocytes (Rag2(-/-)). In this in vivo model, we quantified ?-synuclein aggregation in the substantia nigra (SN) and striatum and determined the numbers of innate and adaptive immune cells in the central nervous system (CNS). The activation state of resident and infiltrated CNS myeloid cells (M1 vs. M2) was further classified by gene and protein expression analyses. The impact of T and B lymphocytes on the phagocytic activity of microglia in the presence of ?-synuclein aggregates was addressed in BV2 microglia in vitro.Compared to WTS(+) Rag2(+/+) mice, where T but not B lymphocytes infiltrated the CNS, decreased amounts of ?-synuclein aggregates were found in WTS(+) Rag2(-/-) mice devoid of mature lymphocytes. The presence of T lymphocytes did not alter the number of Iba1(+) microglia but increased the frequency of the CD11b(+) CD45(hi) population in the CNS, indicative of an increased number of infiltrated macrophages. Moreover, the M1 phenotype was more prominent in WTS(+) Rag2(+/+) mice, whereas the M2 activation state was dominating in the absence of lymphocytes in WTS(+) Rag2(-/-) mice. In vitro, in the presence of T but not B lymphocytes, significantly less ?-synuclein was phagocytosed by BV2 microglia, further supporting the prevalence of the M1 phenotype in the presence of T lymphocytes.Peripheral T lymphocytes strongly contribute to increased ?-synuclein pathology via modulation of CNS myeloid cell function. In the presence of T lymphocytes, microglia phagocytosis of aggregated ?-synuclein is reduced, which increases the severity of synucleinopathy.},
author = {Sommer, Annika and Fadler, Tanja and Dorfmeister, Eva and Hoffmann, Anna-Carin and Xiang, Wei and Winner, Beate and Prots, Iryna},
doi = {10.1186/s12974-016-0632-5},
faupublication = {yes},
journal = {Journal of Neuroinflammation},
note = {EVALuna2:4741},
pages = {174},
peerreviewed = {Yes},
title = {{Infiltrating} {T} lymphocytes reduce myeloid phagocytosis activity in synucleinopathy model},
volume = {13},
year = {2016}
}
@article{faucris.211679652,
abstract = {Mesenchymal stem cells (MSCs) represent key contributors to tissue homeostasis and promising therapeutics for hyperinflammatory conditions including graft-versus-host disease. Their immunomodulatory effects are controlled by microenvironmental signals. The MSCs' functional response towards inflammatory cues is known as MSC-"licensing" and includes indoleamine 2,3-dioxygenase (IDO) upregulation. MSCs use tryptophan-depleting IDO to suppress T-cells. Increasing evidence suggests that several functions are (co-)determined by the cells' metabolic commitment. MSCs are capable of both, high levels of glycolysis and of oxidative phosphorylation. Although several studies have addressed alterations of the immune regulatory phenotype elicited by inflammatory priming metabolic mechanisms controlling this process remain unknown. We demonstrate that inflammatory MSC-licensing causes metabolic shifts including enhanced glycolysis and increased fatty acid oxidation. Yet, only interfering with glycolysis impacts IDO upregulation and impedes T-cell-suppressivity. We identified the Janus kinase (JAK)/signal transducer and activator of transcription (STAT)1 pathway as a regulator of both glycolysis and IDO, and show that enhanced glucose turnover is linked to abundant STAT1 glycosylation. Inhibiting the responsible O-acetylglucosamine (O-GlcNAc) transferase abolishes STAT1 activity together with IDO upregulation. Our data suggest that STAT1-O-GlcNAcylation increases its stability towards degradation thus sustaining downstream effects. This pathway could represent a target for interventions aiming to enhance the MSCs' immunoregulatory potency.},
author = {Jitschin, R. and Böttcher, Martin and Saul, D. and Lukassen, Sören and Bruns, Heiko and Loschinski, Romy and Ekici, Arif Bülent and Reis, André and Mackensen, Andreas and Mougiakakos, Dimitrios},
doi = {10.1038/s41375-018-0376-6},
faupublication = {yes},
journal = {Leukemia},
note = {EVALuna2:35805},
peerreviewed = {Yes},
title = {{Inflammation}-induced glycolytic switch controls suppressivity of mesenchymal stem cells via {STAT1} glycosylation},
year = {2019}
}
@article{faucris.261051150,
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers’ burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients’ CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients’ functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers’ burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers’ burden was high (mean ZBI = 26/88, 0 = no burden, {\_}24 = highly burdened) and correlated with patients’ functional status (rp = -0.555, p < 0.001, n = 242). It was influenced by the CGs’ own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients’ wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs’ depression (rp = 0.627, p < 0.001, n = 234), anxiety (rp = 0.550, p < 0.001, n = 234), and poorer physical condition (rp = -0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients’ impairment in daily routine (rs = -0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs’ lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs’ work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required.},
author = {Schischlevskij, Pavel and Cordts, Isabell and Günther, René and Stolte, Benjamin and Zeller, Daniel and Schröter, Carsten and Weyen, Ute and Regensburger, Martin and Wolf, Joachim and Schneider, Ilka and Hermann, Andreas and Metelmann, Moritz and Kohl, Zacharias and Linker, Ralf A. and Koch, Jan Christoph and Stendel, Claudia and Müschen, Lars H. and Osmanovic, Alma and Binz, Camilla and Klopstock, Thomas and Dorst, Johannes and Ludolph, Albert C. and Boentert, Matthias and Hagenacker, Tim and Deschauer, Marcus and Lingor, Paul and Petri, Susanne and Schreiber-Katz, Olivia},
doi = {10.3390/brainsci11060748},
faupublication = {yes},
journal = {Brain Sciences},
keywords = {Amyotrophic lateral sclerosis (ALS); Anxiety; Caregiver burden; Decreasing autonomy; Depression; Functional status; Health-related quality of life; Informal caregiving; Psychological support; Socioeconomic status},
note = {CRIS-Team Scopus Importer:2021-07-02},
peerreviewed = {Yes},
title = {{Informal} caregiving in amyotrophic lateral sclerosis ({Als}): {A} high caregiver burden and drastic consequences on caregivers’ lives},
volume = {11},
year = {2021}
}
@article{faucris.117396224,
abstract = {Inherited erythromelalgia (IEM) causes debilitating episodic neuropathic pain characterized by burning in the extremities. Inherited "paroxysmal extreme pain disorder" (PEPD) differs in its clinical picture and affects proximal body areas like the rectal, ocular, or jaw regions. Both pain syndromes have been linked to mutations in the voltage-gated sodium channel Nav1.7. Electrophysiological characterization shows that IEM-causing mutations generally enhance activation, whereas mutations leading to PEPD alter fast inactivation. Previously, an A1632E mutation of a patient with overlapping symptoms of IEM and PEPD was reported (Estacion, M., Dib-Hajj, S. D., Benke, P. J., Te Morsche, R. H., Eastman, E. M., Macala, L. J., Drenth, J. P., and Waxman, S. G. (2008) NaV1.7 Gain-of-function mutations as a continuum. A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. J. Neurosci. 28, 11079-11088), displaying a shift of both activation and fast inactivation. Here, we characterize a new mutation of Nav1.7, A1632T, found in a patient suffering from IEM. Although transfection of A1632T in sensory neurons resulted in hyperexcitability and spontaneous firing of dorsal root ganglia (DRG) neurons, whole-cell patch clamp of transfected HEK cells revealed that Nav1.7 activation was unaltered by the A1632T mutation but that steady-state fast inactivation was shifted to more depolarized potentials. This is a characteristic normally attributed to PEPD-causing mutations. In contrast to the IEM/PEPD crossover mutation A1632E, A1632T failed to slow current decay (i.e. open-state inactivation) and did not increase resurgent currents, which have been suggested to contribute to high-frequency firing in physiological and pathological conditions. Reduced fast inactivation without increased resurgent currents induces symptoms of IEM, not PEPD, in the new Nav1.7 mutation, A1632T. Therefore, persistent and resurgent currents are likely to determine whether a mutation in Nav1.7 leads to IEM or PEPD.},
author = {Eberhardt, Mirjam and Nakajima, Julika and Klinger, Alexandra and Neacsu, Cristian and Hühne, Kathrin and o' Reilly, Andrias and Kist, Andreas and Lampe, Anne K. and Fischer, Kerstin and Gibson, Jane and Nau, Carla and Winterpacht, Andreas and Lampert, Angelika},
doi = {10.1074/jbc.M113.502211},
faupublication = {yes},
journal = {Journal of Biological Chemistry},
note = {EVALuna2:2419},
pages = {1971-80},
peerreviewed = {Yes},
title = {{Inherited} pain: sodium channel {Nav1}.7 {A1632T} mutation causes erythromelalgia due to a shift of fast inactivation},
volume = {289},
year = {2014}
}
@article{faucris.209695605,
abstract = {BACKGROUND & AIMS: Intestinal fibrosis is a long-term complication in inflammatory bowel diseases (IBD) frequently resulting in functional damage, bowel obstruction, and surgery. Interleukin 36 (IL36) is a group of cytokines in the IL1 family with inflammatory effects. We studied expression of IL36 and its receptor, interleukin 1 receptor like 2 (IL1RL2 or IL36R) in development of intestinal fibrosis in human tissues and mice.
METHODS: We obtained intestinal tissues from 92 patients with Crohn´s disease (CD), 48 patients with ulcerative colitis (UC), and 26 patients without inflammatory bowel diseases (controls). Tissues were analyzed by histology to detect fibrosis and immunohistochemistry to determine the distribution of fibroblasts and levels of IL36R ligands. Human and mouse fibroblasts were incubated with IL36 or control medium, and transcriptome-wide RNA sequences were analyzed. Mice were given neutralizing antibodies against IL36R and we studied intestinal tissues from Il1rl2-/- mice; colitis and fibrosis was induced in mice by repetitive administration of DSS or TNBS. Bone marrow cells were transplanted from Il1rl2-/- to irradiated wild-type mice and intestinal tissues were analyzed. Antibodies against IL36R were applied to mice with established chronic colitis and fibrosis and intestinal tissues were studied.
RESULTS: Mucosal and submucosal tissues from patients with CD or UC had higher levels of collagens including type VI collagen compared to tissues from controls. In tissues from patients with fibrostenotic CD, significantly higher levels of IL36A were noted, which correlated with high numbers of activated fibroblasts that expressed alpha smooth muscle actin. IL36R activation of mouse and human fibroblasts resulted in expression of genes that regulate fibrosis and tissue remodeling, as well as expression of collagen type VI. Il1rl2-/- mice and mice given injections of an antibody against IL36R developed less severe colitis and fibrosis following administration of DSS or TNBS, but bone marrow cells from Il1rl2-/- mice did not prevent induction of colitis and fibrosis. Injection of antibodies against IL36R significantly reduced established fibrosis in mice with chronic intestinal inflammation.
CONCLUSION: We found higher levels of IL36A in fibrotic intestinal tissues from patients with IBD, compared with controls. IL36 induced expression of genes that regulate fibrogenesis in fibroblasts. Inhibition or knockout of the IL36R in mice reduces chronic colitis and intestinal fibrosis. Agents designed to block IL36R signaling could be developed for prevention and treatment of intestinal fibrosis in patients with IBD.},
author = {Scheibe, Kristina and Kersten, Christina and Schmied, Anabel and Vieth, Michael and Primbs, Tatjana and Carlé, Birgitta-Elisabeth and Knieling, Ferdinand and Claussen, Jing and Klimowicz, Alexander C. and Zheng, Jie and Baum, Patrick and Meyer, Sebastian and Schürmann, Sebastian and Friedrich, Oliver and Waldner, Maximilian and Rath, Timo and Wirtz, Stefan and Kollias, George and Ekici, Arif Bülent and Atreya, Raja and Raymond, Ernest L. and Mbow, M. Lamine and Neurath, Markus and Neufert, Clemens},
doi = {10.1053/j.gastro.2018.11.029},
faupublication = {yes},
journal = {Gastroenterology},
note = {EVALuna2:35123},
peerreviewed = {Yes},
title = {{Inhibiting} {Interleukin} 36 {Receptor} {Signaling} {Reduces} {Fibrosis} in {Mice} with {Chronic} {Intestinal} {Inflammation}},
year = {2018}
}
@article{faucris.123112044,
abstract = {Gain-of-function alterations in several components and modulators of the Ras-MAPK pathway lead to dysregulation of the pathway and cause a broad spectrum of autosomal dominant developmental disorders, collectively known as RASopathies. These findings demonstrate the importance of tight multilevel Ras regulation to safeguard signaling output and prevent aberrant activity. We have recently identified ezrin as a novel regulatory element required for Ras activation. Homozygosity mapping and exome sequencing have now revealed the first presumably disease-causing variant in the coding gene EZR in two siblings with a profound intellectual disability. Localization and membrane targeting of the altered ezrin protein appeared normal but molecular modeling suggested protein interaction surfaces to be disturbed. Functional analysis revealed that the altered ezrin protein is no longer able to bind Ras and facilitate its activation. Furthermore, expression of the altered ezrin protein in different cell lines resulted in abnormal cellular processes, including reduced proliferation and neuritogenesis, thus revealing a possible mechanism for its phenotype in humans. To our knowledge, this is the first report of an autosomal recessively inherited loss-of-function mutation causing reduced Ras activity and thus extends and complements the pathogenicity spectrum of known Ras-MAPK pathway disturbances.},
author = {Riecken, Lars Bjoern and Tawamie, Hasan and Dornblut, Carsten and Buchert, Rebecca and Ismayel, Amina and Schulz, Alexander and Schumacher, Johannes and Sticht, Heinrich and Pohl, Katja J. and Cui, Yan and Reis, André and Morrison, Helen and Abou Jamra, Rami},
doi = {10.1002/humu.22737},
faupublication = {yes},
journal = {Human Mutation},
note = {EVALuna2:9253},
pages = {270-8},
peerreviewed = {Yes},
title = {{Inhibition} of {RAS} activation due to a homozygous ezrin variant in patients with profound intellectual disability},
volume = {36},
year = {2015}
}
@article{faucris.204711933,
abstract = {BACKGROUND: Decapping of mRNA is an important step in the regulation of mRNA turnover and therefore of gene expression, which is a key process controlling development and homeostasis of all organisms. It has been shown that EDC3 plays a role in mRNA decapping, however its function is not well understood. Previously, we have associated a homozygous variant in EDC3 with autosomal recessive intellectual disability. Here, we investigate the functional role of EDC3.
METHODS: We performed transcriptome analyses in patients' samples. In addition, we established an EDC3 loss-of-function model using siRNA-based knockdown in the human neuroblastoma cell line SKNBE and carried out RNA sequencing. Integrative bioinformatics analyses were performed to identify EDC3-dependent candidate genes and/or pathways.
RESULTS: Our analyses revealed that 235 genes were differentially expressed in patients versus controls. In addition, AU-rich element (ARE)-containing mRNAs, whose degradation in humans has been suggested to involve EDC3, had higher fold changes than non-ARE-containing genes. The analysis of RNA sequencing data from the EDC3 in vitro loss-of-function model confirmed the higher fold changes of ARE-containing mRNAs compared to non-ARE-containing mRNAs and further showed an upregulation of long non-coding and coding RNAs. In total, 764 genes were differentially expressed. Integrative bioinformatics analyses of these genes identified dysregulated candidate pathways, including pathways related to synapses/coated vesicles and DNA replication/cell cycle.
CONCLUSION: Our data support the involvement of EDC3 in mRNA decay, including ARE-containing mRNAs, and suggest that EDC3 might be preferentially involved in the degradation of long coding and non-coding RNAs. Furthermore, our results associate ECD3 loss-of-function with synapses-related pathways. Collectively, our data provide novel information that might help elucidate the molecular mechanisms underlying the association of intellectual disability with the dysregulation of mRNA degradation.},
author = {Scheller, Ute and Pfisterer, Kathrin and Uebe, Steffen and Ekici, Arif Bülent and Reis, André and Jamra, Rami and Ferrazzi, Fulvia},
doi = {10.1186/s12920-018-0358-6},
faupublication = {yes},
journal = {Bmc Medical Genomics},
note = {EVALuna2:34136},
peerreviewed = {Yes},
title = {{Integrative} bioinformatics analysis characterizing the role of {EDC3} in {mRNA} decay and its association to intellectual disability},
volume = {11},
year = {2018}
}
@article{faucris.221139909,
abstract = {Intellectual disability (ID) and autism spectrum disorders (ASD) are frequently co-occurring neurodevelopmental disorders and affect 2-3% of the population. Rapid advances in exome and genome sequencing have increased the number of known implicated genes by threefold, to more than a thousand. The main challenges in the field are now to understand the various pathomechanisms associated with this bewildering number of genetic disorders, to identify new genes and to establish causality of variants in still-undiagnosed cases, and to work towards causal treatment options that so far are available only for a few metabolic conditions. To meet these challenges, the research community needs highly efficient model systems. With an increasing number of relevant assays and rapidly developing novel methodologies, the fruit fly Drosophila melanogaster is ideally positioned to change gear in ID and ASD research. The aim of this Review is to summarize some of the exciting work that already has drawn attention to Drosophila as a model for these disorders. We highlight well-established ID-and ASD-relevant fly phenotypes at the (sub) cellular, brain and behavioral levels, and discuss strategies of how this extraordinarily efficient and versatile model can contribute to 'next generation' medical genomics and to a better understanding of these disorders.},
author = {Coll-Tane, Mireia and Krebbers, Alina and Castells-Nobau, Anna and Zweier, Christiane and Schenck, Annette},
doi = {10.1242/dmm.039180},
faupublication = {yes},
journal = {Disease Models & Mechanisms},
note = {CRIS-Team WoS Importer:2019-06-21},
peerreviewed = {Yes},
title = {{Intellectual} disability and autism spectrum disorders 'on the fly': insights from {Drosophila}},
volume = {12},
year = {2019}
}
@article{faucris.269446202,
abstract = {Parkinson’s disease (PD) is neuropathologically characterized by the loss of dopaminergic neurons and the deposition of aggregated alpha synuclein (aSyn). Mounting evidence suggests that neuritic degeneration precedes neuronal loss in PD. A possible underlying mechanism could be the interference of aSyn with microtubule organization in the neuritic development, as implied by sev-eral studies using cell-free model systems. In this study, we investigate the impact of aSyn on mi-crotubule organization in aSyn overexpressing H4 neuroglioma cells and midbrain dopaminergic neuronal cells (mDANs) generated from PD patient-derived human induced pluripotent stem cells (hiPSCs) carrying an aSyn gene duplication (SNCADupl). An unbiased mass spectrometric analysis reveals a preferential binding of aggregated aSyn conformers to a number of microtubule elements. We confirm the interaction of aSyn with beta tubulin III in H4 and hiPSC-derived mDAN cell model systems, and demonstrate a remarkable redistribution of tubulin isoforms from the soluble to insoluble fraction, accompanied by a significantly increased insoluble aSyn level. Concordantly, SNCA-Dupl mDANs show impaired neuritic phenotypes characterized by perturbations in neurite initiation and outgrowth. In summary, our findings suggest a mechanistic pathway, through which aSyn aggregation interferes with microtubule organization and induces neurite impairments.},
author = {Schneider, Yanni and Drobny, Alice and Prots, Iryna and Zunke, Friederike and Xiang, Wei and Seebauer, Lukas and Schneider, Yanni and Drobny, Alice and Ploetz, Sonja and Koudelka, Tomas and Tholey, Andreas and Prots, Iryna and Winner, Beate and Zunke, Friederike and Winkler, Jürgen and Xiang, Wei},
doi = {10.3390/ijms23031812},
faupublication = {yes},
journal = {International Journal of Molecular Sciences},
keywords = {Alpha-synuclein; IPSC; Microtubule; Neurite; Neurodegeneration; Parkinson’s disease; SNCA duplication},
note = {CRIS-Team Scopus Importer:2022-02-11},
peerreviewed = {Yes},
title = {{Interaction} of {Alpha} {Synuclein} and {Microtubule} {Organization} {Is} {Linked} to {Impaired} {Neuritic} {Integrity} in {Parkinson}’s {Patient}-{Derived} {Neuronal} {Cells}},
volume = {23},
year = {2022}
}
@article{faucris.246372231,
abstract = {Dendritic dysfunction is an early event in α-synuclein (α-syn) mediated neurodegeneration. Altered postsynaptic potential and loss of dendritic spines have been observed in different in vitro and in vivo models of synucleinopathies. The integration of newborn neurons into the hippocampus offers the possibility to study dendrite and spine formation in an adult environment. Specifically, survival of hippocampal adult newborn neurons is regulated by synaptic input and was reduced in a mouse model transgenic for human A53T mutant α-syn. We thus hypothesized that dendritic integration of newborn neurons is impaired in the adult hippocampus of A53T mice. We analyzed dendritic morphology of adult hippocampal neurons 1 month after retroviral labeling. Dendrite length was unchanged in the dentate gyrus of A53T transgenic mice. However, spine density and mushroom spine density of newborn neurons were severely decreased. In this mouse model, transgenic α-syn was expressed both within newborn neurons and within their environment. To specifically determine the cell autonomous effects, we analyzed cell-intrinsic overexpression of A53T α-syn using a retrovirus. Since A53T α-syn overexpressing newborn neurons exhibited decreased spine density 1 month after labeling, we conclude that cell-intrinsic A53T α-syn impairs postsynaptic integration of adult hippocampal newborn neurons. Our findings further support the role of postsynaptic degeneration as an early feature in synucleinopathies and provide a model system to study underlying mechanisms.},
author = {Regensburger, Martin and Stemick, Judith and Masliah, Eliezer and Kohl, Zacharias and Winner, Beate},
doi = {10.3389/fcell.2020.561963},
faupublication = {yes},
journal = {Frontiers in Cell and Developmental Biology},
keywords = {A53T alpha-synuclein; adult neurogenesis; cell autonomous; hippocampus; spines},
note = {CRIS-Team Scopus Importer:2020-12-04},
peerreviewed = {Yes},
title = {{Intracellular} {A53T} {Mutant} α-{Synuclein} {Impairs} {Adult} {Hippocampal} {Newborn} {Neuron} {Integration}},
volume = {8},
year = {2020}
}
@article{faucris.121405064,
abstract = {Myelin loss is a widespread neuropathological hallmark of the atypical parkinsonian disorder multiple system atrophy (MSA). On a cellular level, MSA is characterized by alpha-synuclein (aSyn)-positive glial cytoplasmic inclusions (GCIs) within mature oligodendrocytes leading to demyelination as well as axonal and neuronal loss. Oligodendrocyte progenitor cells (OPCs) represent a proliferative cell population distributed throughout the adult mammalian central nervous system. During remyelination, OPCs are recruited to sites of demyelination, differentiate, and finally replace dysfunctional mature oligodendrocytes. However, comprehensive studies investigating OPCs and remyelination processes in MSA are lacking. In the present study, we therefore investigate the effect of human aSyn (h-aSyn) on early primary rat OPC maturation. Upon lentiviral transduction, h-aSyn expressing OPCs exhibit fewer and shorter primary processes at the initiation of differentiation. Until day 4 of a 6day differentiation paradigm, h-aSyn expressing OPCs further show a severely delayed maturation evidenced by reduced myelin gene expression and increased levels of the progenitor marker platelet derived growth factor receptor-alpha (PDGFR?). Matching these results, OPCs that take up extracellular recombinant h-aSyn exhibit a similar delayed differentiation. In both experimental setups however, myelin gene expression is restored at day 6 of differentiation paralleled by decreased intracellular h-aSyn levels indicating a reverse correlation of h-aSyn and the differentiation potential of OPCs. Taken together, these findings suggest a tight link between the intracellular level of h-aSyn and maturation capacity of primary OPCs.},
author = {Ettle, Benjamin and Reiprich, Simone and Deußer, Janina and Schlachetzki, Johannes and Xiang, Wei and Prots, Iryna and Masliah, Eliezer and Winner, Beate and Wegner, Michael and Winkler, Jürgen},
doi = {10.1016/j.mcn.2014.06.012},
faupublication = {yes},
journal = {Molecular and Cellular Neuroscience},
note = {EVALuna2:4696},
pages = {68-78},
peerreviewed = {Yes},
title = {{Intracellular} alpha-synuclein affects early maturation of primary oligodendrocyte progenitor cells},
volume = {62},
year = {2014}
}
@inproceedings{faucris.274481954,
address = {LONDON},
author = {Gumuslu, Esen and Guemues, Evren and Oz, Ozlem and Ozkan, Melis and Karaer, Kadri and Ekici, Arif Bülent and Yildiz, Edibe Pembegul and Aydinli, Nur and Wiesmann da Silva Reis, André},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2022-05-06},
pages = {247-247},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Investigating} consanguineous families from {Turkey} to identify autosomal recessive neurodevelopmental disorders},
year = {2022}
}
@inproceedings{faucris.248104222,
address = {LONDON},
author = {Bosch, Elisabeth and Lukassen, S. and Gregor, Anne and Ekici, Arif Bülent and Zweier, Christiane and Winterpacht, Andreas},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {178-178},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Investigating} {PHF13} induced infertility through single cell transcriptomics and non-vertebrate model organisms},
year = {2020}
}
@inproceedings{faucris.265056566,
address = {ROCKVILLE},
author = {Matthaei, Mario and Clahsen, Thomas and Büttner, Christian and Siebelmann, Sebastian and Heindl, Ludwig and Bachmann, Bjoern and Cursiefen, Claus and Hribek, Agathe},
booktitle = {INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-10-15},
peerreviewed = {unknown},
publisher = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
title = {{Investigating} the role of the fibrillar layer in {Fuchs} endothelial corneal dystrophy},
year = {2021}
}
@article{faucris.274496266,
abstract = {The aggregation of proteins into oligomers and amyloid fibrils is characteristic of several neurodegenerative diseases, including Parkinson disease (PD). In PD, the process of aggregation of ?-synuclein (?-syn) from monomers, via oligomeric intermediates, into amyloid fibrils is considered the disease-causative toxic mechanism. We developed ?-syn mutants that promote oligomer or fibril formation and tested the toxicity of these mutants by using a rat lentivirus system to investigate loss of dopaminergic neurons in the substantia nigra. The most severe dopaminergic loss in the substantia nigra is observed in animals with the ?-syn variants that form oligomers (i.e., E57K and E35K), whereas the ?-syn variants that form fibrils very quickly are less toxic. We show that ?-syn oligomers are toxic in vivo and that ?-syn oligomers might interact with and potentially disrupt membranes.},
author = {Winner, Beate and Jappelli, Roberto and Maji, Samir K. and Desplats, Paula A. and Boyer, Leah and Aigner, Stefan and Hetzer, Claudia and Loher, Thomas and Vilar, Marcal and Campioni, Silvia and Tzitzilonis, Christos and Soragni, Alice and Jessberger, Sebastian and Mira, Helena and Consiglio, Antonella and Pham, Emiley and Masliah, Eliezer and Gage, Fred H. and Riek, Roland},
doi = {10.1073/pnas.1100976108},
faupublication = {yes},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
note = {EVALuna2:26218},
pages = {4194-9},
peerreviewed = {Yes},
title = {{In} vivo demonstration that alpha-synuclein oligomers are toxic.},
volume = {108},
year = {2011}
}
@article{faucris.230054571,
abstract = {Kiechle et al. present two transgenic mouse models that allow direct quantitative and spatial detection of α-synuclein (α-syn) oligomers in vivo. They demonstrate α-syn aggregation at the synapse, age-dependent accumulation of 8–16-mer α-syn oligomer species, and trans-cellular oligomer spreading from forebrain to hindbrain neurons.},
author = {Kiechle, Martin and von Einem, Bjoern and Höfs, Lennart and Voehringer, Patrizia and Grozdanov, Veselin and Markx, Daniel and Parlato, Rosanna and Wiesner, Diana and Mayer, Benjamin and Sakk, Olena and Baumann, Bernd and Lukassen, Sören and Liss, Birgit and Ekici, Arif Bülent and Ludolph, Albert C. and Walther, Paul and Ferger, Boris and McLean, Pamela J. and Falkenburger, Björn H. and Weishaupt, Jochen H. and Danzer, Karin M.},
doi = {10.1016/j.celrep.2019.10.089},
faupublication = {yes},
journal = {Cell Reports},
keywords = {aging; alpha-synuclein; neurodegeneration; oligomerization; Parkinson's disease; progressive phenotype; protein-fragment complementation; spreading; synaptic oligomers; transgenic mouse model},
note = {CRIS-Team Scopus Importer:2019-12-03},
pages = {2862-2874.e9},
peerreviewed = {Yes},
title = {{In} {Vivo} {Protein} {Complementation} {Demonstrates} {Presynaptic} α-{Synuclein} {Oligomerization} and {Age}-{Dependent} {Accumulation} of 8–16-mer {Oligomer} {Species}},
volume = {29},
year = {2019}
}
@article{faucris.236673415,
abstract = {Background: Oral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation require dose adjustment based on certain clinical criteria, but the off-label use of the reduced doses is common. Methods: Data from an observational registry including patients admitted with acute cerebral ischemia while taking oral Factor Xa inhibitors for atrial fibrillation between April 2016 and December 2018 were investigated. The dose regimen of the Xa inhibitor was classified as “appropriate”, “underdosed” and “overdosed” in conformity with the European Medicines Agency labelling. The effect of underdosing on the functional factor Xa plasma level on admission, the clinical stroke severity and the functional outcome after 3 months were investigated. Results: 254 patients with cerebral ischemia while on Factor Xa inhibitors were included. The dose regimen of the Factor Xa inhibitor was appropriate in 166 patients (65%), underdosed in 67 patients (26%) and overdosed in 21 patients (8%). Underdosing was associated with female sex, diabetes mellitus and higher CHA2DS2–Vasc scores. Underdosing independently predicted lower anti-Xa plasma levels on admission [median 69.4 ng/ml (IQR 0.0–121.6) vs. 129.2 ng/ml (65.5–207.2); p < 0.001], was associated with higher NIHSS scores on admission [median 5 (IQR 1–10) vs. 3 (1–7); p = 0.041] and worse functional outcome after 3 months (favorable outcome 26.9% vs. 46.9%; p = 0.025). Conclusion: One in three patients with ischemic stroke during treatment with oral Xa inhibitors used inappropriate dose regimens. Underdosing was associated with lower functional plasma levels, higher clinical stroke severity and worse functional outcome.},
author = {Stoll, Svenja and Macha, Kosmas and Marsch, Armin and Gerner, Stefan and Siedler, Gabriela and Fröhlich, Kilian and Volbers, Bastian and Strasser, Erwin and Schwab, Stefan and Kallmünzer, Bernd},
doi = {10.1007/s00415-020-09795-3},
faupublication = {yes},
journal = {Journal of Neurology},
keywords = {Atrial fibrillation; Direct oral anticoagulants; Dose reduction; Plasma levels; Stroke},
note = {CRIS-Team Scopus Importer:2020-03-31},
peerreviewed = {Yes},
title = {{Ischemic} stroke and dose adjustment of oral {Factor} {Xa} inhibitors in patients with atrial fibrillation},
year = {2020}
}
@article{faucris.242198743,
abstract = {Hereditary spastic paraplegia (HSP) is a heterogeneous group of rare motor neuron disorders characterized by progressive weakness and spasticity of the lower limbs. HSP type 11 (SPG11-HSP) is linked to pathogenic variants in the SPG11 gene and it represents the most frequent form of complex autosomal recessive HSP. The majority of SPG11-HSP patients exhibit additional neurological symptoms such as cognitive decline, thin corpus callosum, and peripheral neuropathy. Yet, the mechanisms of SPG11-linked spectrum diseases are largely unknown. Recent findings indicate that spatacsin, the 280 kDa protein encoded by SPG11, may impact the autophagy-lysosomal machinery. In this update, we summarize the current knowledge of SPG11-HSP. In addition to clinical symptoms and differential diagnosis, our work aims to link the different clinical manifestations with the respective structural abnormalities and cellular in vitro phenotypes. Moreover, we describe the impact of localization and function of spatacsin in different neuronal systems. Ultimately, we propose a model in which spatacsin bridges between neurodevelopmental and neurodegenerative phenotypes of SPG11-linked disorders.},
author = {Pozner, Tatyana and Regensburger, Martin and Engelhorn, Tobias and Winkler, Jürgen and Winner, Beate},
doi = {10.1093/brain/awaa099},
faupublication = {yes},
journal = {Brain},
keywords = {autophagy; hereditary spastic paraplegia; neurodegeneration; neurodevelopment; SPG11},
note = {CRIS-Team Scopus Importer:2020-09-04},
pages = {2369-2379},
peerreviewed = {Yes},
title = {{Janus}-faced spatacsin ({SPG11}): involvement in neurodevelopment and multisystem neurodegeneration},
volume = {143},
year = {2020}
}
@article{faucris.111759384,
abstract = {The transforming growth factor-? (TGF-?) family member activin A exerts multiple neurotrophic and protective effects in the brain. Activin also modulates cognitive functions and affective behavior and is a presumed target of antidepressant therapy. Despite its important role in the injured and intact brain, the mechanisms underlying activin effects in the CNS are still largely unknown. Our goal was to identify the first target genes of activin signaling in the hippocampus in vivo. Electroconvulsive seizures, a rodent model of electroconvulsive therapy in humans, were applied to C57BL/6J mice to elicit a strong increase in activin A signaling. Chromatin immunoprecipitation experiments with hippocampal lysates subsequently revealed that binding of SMAD2/3, the intracellular effectors of activin signaling, was significantly enriched at the Pmepa1 gene, which encodes a negative feedback regulator of TGF-? signaling in cancer cells, and at the Kdm6b gene, which encodes an epigenetic regulator promoting transcriptional plasticity. Underlining the significance of these findings, activin treatment also induced PMEPA1 and KDM6B expression in human forebrain neurons generated from embryonic stem cells suggesting interspecies conservation of activin effects in mammalian neurons. Importantly, physiological stimuli such as provided by environmental enrichment proved already sufficient to engender a rapid and significant induction of activin signaling concomitant with an upregulation of Pmepa1 and Kdm6b expression. Taken together, our study identified the first target genes of activin signaling in the brain. With the induction of Kdm6b expression, activin is likely to gain impact on a presumed epigenetic regulator of activity-dependent neuronal plasticity.},
author = {Link, Andrea and Kurinna, Svitlana and Havlicek, Steven and Lehnert, Sandra and Reichel, Martin and Kornhuber, Johannes and Winner, Beate and Huth, Tobias and Zheng, Fang and Werner, Sabine and Alzheimer, Christian},
doi = {10.1007/s12035-015-9363-3},
faupublication = {yes},
journal = {Molecular Neurobiology},
note = {EVALuna2:2488},
pages = {4210-25},
peerreviewed = {Yes},
title = {{Kdm6b} and {Pmepa1} as {Targets} of {Bioelectrically} and {Behaviorally} {Induced} {Activin} {A} {Signaling}},
volume = {53},
year = {2016}
}
@article{faucris.213880799,
abstract = {To date, the genes associated with Psoriatic Arthritis (PsA) are principally involved in inflammation, immune response and epidermal differentiation, without any information about the relationship between disease and bone metabolism genes. Our work was focused on 5q31 locus, which contains several genetic variants significantly associated with PsA. The study involved 1526 subjects (500 PsA, 426 PsV, 600 controls). The region was evaluated by selecting and genotyping the SNPs of interest by Real Time PCR and direct sequencing. The results were subjected to biostatistic and bioinformatic analysis. The case-control study highlighted a significant association between KIF3A/IL-4 and PsA, but not with PsV (Psoriasis Vulgaris) patients. In addition, the haplotype analysis revealed two haplotypes significantly associated with PsA susceptibility. The Linkage Disequilibrium (LD) study showed the presence of a specific block in high LD within 132,692,628-132,737,638 bp of 5q31, giving additional evidence of specific association of the 5q31 region in PsA patients. Moreover, KIF3A expression was assessed by immunohistochemistry assays which showed a marked and significant difference of KIF3A expression between pathological and normal tissues. Our analysis described KIF3A and IL-4 as novel susceptibility genes for PsA, suggesting a clear implication of bone metabolism genes in the disease etiopathogenesis.},
author = {Cascella, Raffaella and Strafella, Claudia and Ragazzo, Michele and Manzo, Laura and Costanza, Gaetana and Bowes, John and Hueffmeier, Ulrike and Potenza, Saverio and Sangiuolo, Federica and Reis, André and Barton, Anne and Novelli, Giuseppe and Orlandi, Augusto and Giardina, Emiliano},
doi = {10.18632/oncotarget.20727},
faupublication = {yes},
journal = {Oncotarget},
note = {EVALuna2:9386},
pages = {95401-95411},
peerreviewed = {Yes},
title = {{KIF3A} and {IL}-4 are disease-specific biomarkers for psoriatic arthritis susceptibility},
volume = {8},
year = {2017}
}
@article{faucris.225627248,
author = {Huchzermeyer, Cord and Pasutto, Francesca and Wiesmann da Silva Reis, André and Kremers, Jan},
faupublication = {yes},
journal = {Investigative Ophthalmology & Visual Science},
peerreviewed = {Yes},
title = {{L}- and {M}-cone driven temporal contrast sensitivity is reduced at low frequencies in patients with {Stargardt}'s disease},
volume = {58},
year = {2017}
}
@article{faucris.106308004,
abstract = {Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NF?B cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8(+) T-cells and CD4(+) T-cells including TH0, TH1 and TH17). The identified loci explain ~28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10(-89)). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.},
author = {Tsoi, Lam C. and Stuart, Philip E. and Tian, Chao and Gudjonsson, Johann E. and Das, Sayantan and Zawistowski, Matthew and Ellinghaus, Eva and Barker, Jonathan N. and Chandran, Vinod and Dand, Nick and Duffin, Kristina Callis and Enerback, Charlotta and Esko, Tonu and Franke, Andre and Gladman, Dafna D. and Hoffmann, Per and Kingo, Kulli and Koks, Sulev and Krueger, Gerald G. and Lim, Henry W. and Metspalu, Andres and Mrowietz, Ulrich and Mucha, Soren and Rahman, Proton and Reis, André and Tejasvi, Trilokraj and Trembath, Richard and Voorhees, John J. and Weidinger, Stephan and Weichenthal, Michael and Wen, Xiaoquan and Eriksson, Nicholas and Kang, Hyun M. and Hinds, David A. and Nair, Rajan P. and Abecasis, Goncalo R. and Elder, James T.},
doi = {10.1038/ncomms15382},
faupublication = {yes},
journal = {Nature Communications},
note = {EVALuna2:9373},
pages = {15382},
peerreviewed = {Yes},
title = {{Large} scale meta-analysis characterizes genetic architecture for common psoriasis associated variants},
volume = {8},
year = {2017}
}
@article{faucris.109179444,
abstract = {There is increasing interest in the introduction of public health policies relating to latent tuberculous infection (LTBI). However, there has been little previous systematic engagement with LTBI from an ethical perspective. This article offers a general overview of ethical issues in relation to LTBI, with particular focus on those aspects relevant to the development and implementation of public health policy. Key characteristics of LTBI are discussed from an ethical perspective, with examples of challenging situations for policy makers.},
author = {Denholm, J. T. and Matteelli, Alberto and Reis, André},
doi = {10.5588/ijtld.14.0543},
faupublication = {yes},
journal = {International Journal of Tuberculosis and Lung Disease},
note = {EVALuna2:5665},
pages = {137-40},
peerreviewed = {Yes},
title = {{Latent} tuberculous infection: ethical considerations in formulating public health policy},
volume = {19},
year = {2015}
}
@article{faucris.108510644,
abstract = {MLL fusions are leukemogenic transcription factors that enhance transcriptional elongation through modification of chromatin and RNA Pol II. Global transcription rates and chromatin changes accompanying the transformation process induced by MLL-ENL were monitored by nascent RNA-seq and ChIP-seq, revealing 165 direct target genes separated into two distinct clades. ME5 genes bound MLL-ENL at the promoter, relied on DOT1L-mediated histone methylation, and coded preferentially for transcription factors, including many homeobox genes. A distinct ME3 group accumulated MLL-ENL beyond the termination site, was dependent on P-TEFb-mediated phosphorylation of RNA Pol II for transcription, and translated mainly into proteins involved in RNA biology and ribosome assembly. This dichotomy was reflected by a differential sensitivity toward small molecule inhibitors, suggesting the possibility of a combinatorial strategy for treatment of MLL-induced leukemia.},
author = {Garcia-Cuellar, Maria-Paz and Büttner, Christian and Bartenhagen, Christoph and Dugas, Martin and Slany, Robert},
doi = {10.1016/j.celrep.2016.03.018},
faupublication = {yes},
journal = {Cell Reports},
keywords = {Chromatin; DOT1L; Inhibitors; Leukemia; MLL-ENL; P-TEFb},
pages = {310-322},
peerreviewed = {Yes},
title = {{Leukemogenic} {MLL}-{ENL} {Fusions} {Induce} {Alternative} {Chromatin} {States} to {Drive} a {Functionally} {Dichotomous} {Group} of {Target} {Genes}},
volume = {15},
year = {2016}
}
@article{faucris.307272555,
abstract = {Purpose: LHX2 encodes the LIM homeobox 2 transcription factor (LHX2), which is highly expressed in brain and well conserved across species, but it has not been clearly linked to neurodevelopmental disorders (NDDs) to date. Methods: Through international collaboration, we identified 19 individuals from 18 families with variable neurodevelopmental phenotypes, carrying a small chromosomal deletion, likely gene-disrupting or missense variants in LHX2. Functional consequences of missense variants were investigated in cellular systems. Results: Affected individuals presented with developmental and/or behavioral abnormalities, autism spectrum disorder, variable intellectual disability, and microcephaly. We observed nucleolar accumulation for 2 missense variants located within the DNA-binding HOX domain, impaired interaction with co-factor LDB1 for another variant located in the protein-protein interaction–mediating LIM domain, and impaired transcriptional activation by luciferase assay for 4 missense variants. Conclusion: We implicate LHX2 haploinsufficiency by deletion and likely gene-disrupting variants as causative for a variable NDD. Our findings suggest a loss-of-function mechanism also for likely pathogenic LHX2 missense variants. Together, our observations underscore the importance of LHX2 in the nervous system and for variable neurodevelopmental phenotypes.},
author = {Schmid, Cosima M. and Gregor, Anne and Costain, Gregory and Morel, Chantal F. and Massingham, Lauren and Schwab, Jennifer and Quélin, Chloé and Faoucher, Marie and Kaplan, Julie and Procopio, Rebecca and Saunders, Carol J. and Cohen, Ana S.A. and Lemire, Gabrielle and Sacharow, Stephanie and O'Donnell-Luria, Anne and Segal, Ranit Jaron and Kianmahd Shamshoni, Jessica and Schweitzer, Daniela and Ebrahimi-Fakhari, Darius and Monaghan, Kristin and Palculict, Timothy Blake and Napier, Melanie P. and Tao, Alice and Isidor, Bertrand and Moradkhani, Kamran and Reis, André and Sticht, Heinrich and Chung, Wendy K. and Zweier, Christiane},
doi = {10.1016/j.gim.2023.100839},
faupublication = {yes},
journal = {Genetics in Medicine},
keywords = {ASD; Intellectual disability; LHX2; Microcephaly; NDD; Neurodevelopmental disorder},
note = {CRIS-Team Scopus Importer:2023-07-07},
peerreviewed = {Yes},
title = {{LHX2} haploinsufficiency causes a variable neurodevelopmental disorder},
volume = {25},
year = {2023}
}
@article{faucris.221883053,
abstract = {Purpose: Identifying and characterizing novel causes of autosomal recessive intellectual disability based on systematic clinical and genetic evaluation, followed by functional experiments. Methods: Clinical examinations, genome-wide positional mapping, and sequencing were followed by quantitative polymerase chain reaction and western blot of the protein SVBP and its interaction partners. We then knocked down the gene in rat primary hippocampal neurons and evaluated the consequences on synapses. Results: We identified a founder, homozygous stop-gain variant in SVBP (c.82C>T; p.[Gln28*]) in four affected individuals from two independent families with intellectual disability, microcephaly, ataxia, and muscular hypotonia. SVBP encodes a small chaperone protein that transports and stabilizes two angiogenesis regulators, VASH1 and VASH2. The altered protein is unstable and nonfunctional since transfected HeLa cells with mutant SVBP did not reveal evidence for immunoreactive SVBP protein fragments and cotransfection with VASH1 showed a severe reduction of VASH1 in medium and cell lysate. Knocking down Svbp in rat primary hippocampal neurons led to a significant decrease in the number of excitatory synapses. Conclusion: SVBP is not only involved in angiogenesis, but also has vital functions in the central nervous system. Biallelic loss-of-function variants in SVBP lead to intellectual disability.},
author = {Iqbal, Zafar and Tawamie, Hasan and Ba, Wei and Reis, André and Halak, Bassam Al and Sticht, Heinrich and Uebe, Steffen and Kasri, Nael Nadif and Riazuddin, Sheikh and van Bokhoven, Hans and Abou Jamra, Rami},
doi = {10.1038/s41436-018-0415-8},
faupublication = {yes},
journal = {Genetics in Medicine},
keywords = {CCD23; hippocampal neurons; intellectual disability; NGS; VASH1},
note = {CRIS-Team Scopus Importer:2019-07-09},
peerreviewed = {Yes},
title = {{Loss} of function of {SVBP} leads to autosomal recessive intellectual disability, microcephaly, ataxia, and hypotonia},
year = {2019}
}
@article{faucris.245133241,
abstract = {Pathogenic variants in PHD finger protein 6 (PHF6) cause Borjeson–Forssman–Lehmann syndrome (BFLS), a rare X-linked neurodevelopmental disorder, which manifests variably in both males and females. To investigate the mechanisms behind overlapping but distinct clinical aspects between genders, we assessed the consequences of individual variants with structural modelling and molecular techniques. We found evidence that de novo variants occurring in females are more severe and result in loss of PHF6, while inherited variants identified in males might be hypomorph or have weaker effects on protein stability. This might contribute to the different phenotypes in male versus female individuals with BFLS. Furthermore, we used CRISPR/Cas9 to induce knockout of PHF6 in SK-N-BE (2) cells which were then differentiated to neuron-like cells in order to model nervous system related consequences of PHF6 loss. Transcriptome analysis revealed a broad deregulation of genes involved in chromatin and transcriptional regulation as well as in axon and neuron development. Subsequently, we could demonstrate that PHF6 is indeed required for proper neuron proliferation, neurite outgrowth and migration. Impairment of these processes might therefore contribute to the neurodevelopmental and cognitive dysfunction in BFLS.},
author = {Fliedner, Anna and Gregor, Anne and Ferrazzi, Fulvia and Ekici, Arif Bülent and Sticht, Heinrich and Zweier, Christiane},
doi = {10.1038/s41598-020-75999-2},
faupublication = {yes},
journal = {Scientific Reports},
note = {CRIS-Team Scopus Importer:2020-11-13},
peerreviewed = {Yes},
title = {{Loss} of {PHF6} leads to aberrant development of human neuron-like cells},
volume = {10},
year = {2020}
}
@article{faucris.274495765,
abstract = {Mutations in the LRRK2 gene are the most common cause of genetic Parkinson's disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations are still not clear, data emerging from in vitro and in vivo models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation.We created mice lacking exon 41 that encodes the activation hinge of the kinase domain of LRRK2. We have performed a comprehensive analysis of these mice up to 20 months of age, including evaluation of dopamine storage, release, uptake and synthesis, behavioral testing, dendritic spine and proliferation/neurogenesis analysis.Our results show that the dopaminergic system was not functionally comprised in LRRK2 knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than their wild type littermates on the accelerated rod during rotarod testing. Finally, we confirm that loss of LRRK2 caused degeneration in the kidney, accompanied by a progressive enhancement of autophagic activity and accumulation of autofluorescent material, but without evidence of biphasic changes.},
author = {Winner, Beate and Prots, Iryna and Hinkle, Kelly M and Yue, Mei and Bahareh, Behrouz and Dächsel, Justus C and Lincoln, Sarah J and Bowles, Erin E and Beevers, Joel E and Dugger, Brittany and Kent, Caroline B and Nishioka, Kenya and Lin, Wen-Lang and Dickson, Dennis W. and Janus, Christopher J and Farrer, Matthew and Melrose, Heather L},
doi = {10.1186/1750-1326-7-25},
faupublication = {yes},
journal = {Molecular Neurodegeneration},
keywords = {Parkinson’s disease, Knockout, Dopamine, Microdialysis, Neuropathology, Open-field, Motor co-ordination, Kidney, Autophagy},
note = {EVALuna2:26219},
pages = {25},
peerreviewed = {Yes},
title = {{LRRK2} knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors.},
url = {https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/1750-1326-7-25#author-information},
volume = {7},
year = {2012}
}
@article{faucris.251031563,
abstract = {Background Protein-losing enteropathy (PLE) is a severe complication of the Fontan circulation. There is increasing discussion about whether lymphatic dysregulation is involved as pathomechanism of PLE. This investigation focuses on the interplay between alteration of lymphatic cells and immunologic pathway alterations. Methods Micro-ribonucleic acid (miRNA) expression profiling was performed in 49 patients (n = 10 Fontan patients with PLE, n = 30 Fontan patients without PLE, and n = 9 patients with dextro-transposition of the great arteries (dTGA). miRNA pathway analysis was performed to identify significantly enriched pathways. To determine lymphocyte populations and subtypes multiparameter flow cytometry was used. Results miRNAs pathway analysis of Fontan patients with PLE revealed 20 significantly changed networks of which four of the ten largest were associated with immunologic processes. This finding is supported by significant T cell deficiency with decreased CD4+ count (p = 0.0002), altered CD4 +/CD8+ ratio, and significantly modified CD4+ (p < 0.0001) and CD8+ (p = 0.0002) T cell differentiation toward effector and terminal differentiated T cells in Fontan patients with PLE. Analyses of CD4+ T cell subsets demonstrated significantly increased frequencies of CD4+ CD25+ CD127- regulatory T cells (Treg) in Fontan patients with PLE (p = 0.0011). Conclusion PLE in Fontan patients is associated with severe lymphopenia, T cell deficiency, significant alterations of T cell differentiation, and increased Treg frequency reflecting an immune status of chronic inflammation and shortened protection against pathogens and autoimmunity. These cellular alterations seemed to be dysregulated by several miRNA controlled immunological pathways.},
author = {Moosmann, Julia and Toka, Okan and Lukassen, Sören and Ekici, Arif Bülent and Mackensen, Andreas and Dittrich, Sven and Völkl, Simon},
doi = {10.1055/s-0041-1723781},
faupublication = {yes},
journal = {Thoracic and Cardiovascular Surgeon, Supplement},
keywords = {congenital heart disease (CHD); genetics; genomics; inflammation; systemic},
note = {CRIS-Team Scopus Importer:2021-03-05},
pages = {E10-E20},
peerreviewed = {Yes},
title = {{Lymphocyte} {Immune} {Response} and {T} {Cell} {Differentiation} in {Fontan} {Patients} with protein-losing enteropathy},
volume = {69},
year = {2021}
}
@article{faucris.242407736,
abstract = {Abstract: Progressive cyst growth leads to decline of renal function in polycystic kidney disease. Macrophage migration inhibitory factor (MIF) was found to be upregulated in cyst-lining cells in a mouse model of polycystic kidney disease and to promote cyst growth. In addition, MIF can be secreted by tubular cells and may contribute to cyst growth in an autocrine manner. However, the underlying mechanisms leading to induction of MIF in cyst-lining cells remained elusive. Here, we demonstrate that hypoxia-inducible transcription factor (HIF) 1α upregulates MIF in cyst-lining cells in a tubule-specific PKD1 knockout mouse. Pharmacological stabilization of HIF-1α resulted in significant increase of MIF in cyst epithelial cells whereas tubule-specific knockout of HIF-1α prevented MIF upregulation. Identical regulation could be found for ABCA1, which has been shown to act as a transport protein for MIF. Furthermore, we show that MIF and ABCA1 are direct target genes of HIF-1α in human primary tubular cells. Next to HIF-1α and hypoxia, we found MIF being additionally regulated by cAMP which is a strong promotor of cyst growth. In line with these findings, HIF-1α- and cAMP-dependent in vitro cyst growth could be decreased by the MIF-inhibitor ISO-1 which resulted in reduced cyst cell proliferation. In conclusion, HIF-1α and cAMP regulate MIF in primary tubular cells and cyst-lining epithelial cells, and MIF promotes cyst growth in the absence of macrophages. In line with these findings, the MIF inhibitor ISO-1 attenuates HIF-1α- and cAMP-dependent in vitro cyst enlargement. Key messages: • MIF is upregulated in cyst-lining cells in a polycystic kidney disease mouse model. • MIF upregulation is mediated by hypoxia-inducible transcription factor (HIF) 1α. • ABCA1, transport protein for MIF, is also regulated by HIF-1α in vitro and in vivo. • MIF is additionally regulated by cAMP, a strong promotor of cyst growth. • MIF-inhibitor ISO-1 reduces HIF-1α- and cAMP-dependent cyst growth.},
author = {Safi, Wajima and Kraus, Andre and Grampp, Steffen and Schödel, Johannes and Buchholz, Björn},
doi = {10.1007/s00109-020-01964-1},
faupublication = {yes},
journal = {Journal of Molecular Medicine},
keywords = {cAMP; Hypoxia-inducible factor 1α; Macrophage migration inhibitory factor; Polycystic kidney disease},
note = {CRIS-Team Scopus Importer:2020-09-11},
pages = {1547-1559},
peerreviewed = {Yes},
title = {{Macrophage} migration inhibitory factor is regulated by {HIF}-1α and {cAMP} and promotes renal cyst cell proliferation in a macrophage-independent manner},
volume = {98},
year = {2020}
}
@article{faucris.216840828,
abstract = {Immune sensing of Mycobacterium tuberculosis relies on recognition by macrophages. Mycobacterial cord factor, trehalose-6,6-dimycolate (TDM), is the most abundant cell wall glycolipid and binds to the C-type lectin receptor (CLR) MINCLE. To explore the kinase signaling linking the TDM-MINCLE interaction to gene expression, we employed quantitative phosphoproteome analysis. TDM caused upregulation of 6.7% and suppressed 3.8% of the 14,000 phospho-sites identified on 3727 proteins. MINCLE-dependent phosphorylation was observed for canonical players of CLR signaling (e.g. PLC, PKC), and was enriched for PKC and GSK3 kinase motifs. MINCLE-dependent activation of the PI3K-AKT-GSK3 pathway contributed to inflammatory gene expression and required the PI3K regulatory subunit p85. Unexpectedly, a substantial fraction of TDM-induced phosphorylation was MINCLE-independent, a finding paralleled by transcriptome data. Bioinformatics analysis of both data sets concurred in the requirement for MINCLE for innate immune response pathways and processes. In contrast, MINCLE-independent phosphorylation and transcriptome responses were linked to cell cycle regulation. Collectively, our global analyses show substantial reprogramming of macrophages by TDM and reveal a dichotomy of MINCLE-dependent and-independent signaling linked to distinct biological responses.},
author = {Hansen, Madlen and Peltier, Julian and Killy, Barbara and Amin, Bushra and Bodendorfer, Barbara and HäRtlova, Anetta and Uebel, Sebastian and Bosmann, Markus and Hofmann, Jörg and Büttner, Christian and Ekici, Arif Bülent and Kuttke, Mario and Franzyk, Henrik and Foged, Camilla and Beer-Hammer, Sandra and Schabbauer, Gernot and Trost, Matthias and Lang, Roland},
doi = {10.1074/mcp.RA118.000929},
faupublication = {yes},
journal = {Molecular & Cellular Proteomics},
note = {CRIS-Team Scopus Importer:2019-05-02},
pages = {669-685},
peerreviewed = {Yes},
title = {{Macrophage} phosphoproteome analysis reveals {MINCLE}-dependent and-independent mycobacterial cord factor signaling},
volume = {18},
year = {2019}
}
@article{faucris.217476142,
abstract = {Losing one's ability to speak, because of tissue deficiency at the vocal fold (VF), leads to serious impairment in the quality of life. Until now, there is no successful approach for regenerating the VF. The aim of this study was to show the advantage of magnetic nanoparticles in the generation of scaffold-free three-dimensional (3D) VF cell constructs by magnetic tissue engineering (MTE). Rabbit VF fibroblasts were used to establish MTE: after cellular uptake of superparamagnetic iron oxide nanoparticles (SPIONs), cells can be controlled with a magnetic field thereby forming solid 3D cell structures. To transfer this method into human cells, SPIONs were adapted accordingly and tested for their influence on human VF (hVF) cells and for their ability to perform MTE with hVF cells. Of interest, the cell number and the magnet's shape influence the form of the rabbit VF cell construct. After successful characterization of hVF cells, biocompatibility analyses revealed no significant influence of SPIONs on them, thus 3D hVF cell constructs could be successfully generated by MTE. These basic results are important to develop MTE as an innovative method to regenerate functional VFs. We expect that in vivo studies, including MTE as an elegant, far-field controlled and touchless technology, will translate MTE VF bioconstructs into reconstructive laryngeal medicine. Impact Statement This study aims at nanotechnology for regenerative medicine by magnetic tissue engineering (MTE). New approaches for vocal fold (VF) reconstruction are desperately needed. Superparamagnetic iron oxide nanoparticles offer innovative, scaffold-free potentials for tissue engineering: MTE. By using MTE we could generate functional multilayered human VF cell constructs, which can consequently be used to regenerate the voice in patients with VF injuries.},
author = {Poettler, Marina and Fliedner, Anna and Bergmann, Julia and Bui, Linh Katrin and Mühlberger, Marina and Braun, Christian and Graw, Matthias and Janko, Christina and Friedrich, Oliver and Alexiou, Christoph and Lyer, Stefan},
doi = {10.1089/ten.tea.2019.0009},
faupublication = {yes},
journal = {Tissue Engineering: Parts A, B, and C},
note = {CRIS-Team WoS Importer:2019-05-14},
peerreviewed = {Yes},
title = {{Magnetic} {Tissue} {Engineering} of the {Vocal} {Fold} {Using} {Superparamagnetic} {Iron} {Oxide} {Nanoparticles}},
year = {2019}
}
@article{faucris.121739684,
abstract = {Intellectual disability (ID) is one of the most common reasons for referral to genetic counseling. Nevertheless, in over 50% of the cases no diagnosis can be made. Here, we present how exome sequencing in combination with medical genetics evaluation led to the identification of a known pathogenic homozygous mutation in MAN1B1 in a consanguineous Turkish family. The phenotype comprised mild ID, truncal obesity and facial dysmorphism, comparable to that of the patients in the 3 recent publications on mutations in this gene. Clinically, the majority of patients in the literature showed congenital disorder of glycosylation syndrome type 2. In this study, we summarize the current knowledge about MAN1B1 mutations from the literature as well as databases and suggest that exome sequencing should be implemented in a larger scale in routine diagnostics, since autosomal recessive ID has proven to be extremely heterogeneous. Even syndromic patterns may only become recognizable retrospectively.},
author = {Hoffjan, Sabine and Epplen, Jörg T. and Reis, André and Abou Jamra, Rami},
doi = {10.1159/000371399},
faupublication = {yes},
journal = {Molecular Syndromology},
note = {EVALuna2:9262},
pages = {58-62},
peerreviewed = {Yes},
title = {{MAN1B1} {Mutation} {Leads} to a {Recognizable} {Phenotype}: {A} {Case} {Report} and {Future} {Prospects}},
volume = {6},
year = {2015}
}
@inproceedings{faucris.248096284,
address = {LONDON},
author = {Macha, Kosmas and Stoll, Svenja and Siedler, Gabriela and Volbers, Bastian and Strasser, Erwin and Schwab, Stefan and Kallmünzer, Bernd},
booktitle = {INTERNATIONAL JOURNAL OF STROKE},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {277-278},
peerreviewed = {unknown},
publisher = {SAGE PUBLICATIONS LTD},
title = {{MANAGEMENT} {OF} {INSUFFICIENT} {FUNCTIONAL} {ANTITHROMBOTIC} {ACTIVITY} {DURING} {TREATMENT} {WITH} {DIRECT} {ORAL} {ANTICOAGULANTS} {FOR} {STROKE} {PREVENTION}},
year = {2020}
}
@article{faucris.264315761,
abstract = {Cohen-Gibson syndrome is a rare genetic disorder, characterized by fetal or early childhood overgrowth and mild to severe intellectual disability. It is caused by heterozygous aberrations in EED, which encodes an evolutionary conserved polycomb group (PcG) protein that forms the polycomb repressive complex-2 (PRC2) together with EZH2, SUZ12, and RBBP7/4. In total, 11 affected individuals with heterozygous pathogenic variants in EED were reported, so far. All variants affect a few key residues within the EED WD40 repeat domain. By trio exome sequencing, we identified the heterozygous missense variant c.581A > G, p.(Asn194Ser) in exon 6 of the EED-gene in an individual with moderate intellectual disability, overgrowth, and epilepsy. The same pathogenic variant was detected in 2 of the 11 previously reported cases. Epilepsy, however, was only diagnosed in one other individual with Cohen-Gibson syndrome before. Our findings further confirm that the WD40 repeat domain represents a mutational hotspot; they also expand the clinical spectrum of Cohen-Gibson syndrome and highlight the clinical variability even in individuals with the same pathogenic variant. Furthermore, they indicate a possible association between Cohen-Gibson syndrome and epilepsy.},
author = {Hetzelt, Katalin and Winterholler, Martin and Kerling, Frank and Rauch, Christophe and Ekici, Arif Bülent and Winterpacht, Andreas and Vasileiou, Georgia and Uebe, Steffen and Thiel, Christian and Kraus, Cornelia and Reis, André and Zweier, Christiane},
doi = {10.1002/ajmg.a.62496},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
note = {CRIS-Team WoS Importer:2021-09-24},
peerreviewed = {Yes},
title = {{Manifestation} of epilepsy in a patient with {EED}-related overgrowth ({Cohen}-{Gibson} syndrome)},
year = {2021}
}
@article{faucris.205272321,
abstract = {Previous identification of the inducible nitric oxide synthase (NOS2) gene as a risk allele for psoriasis (Ps) and psoriatic arthritis (PsA) suggests a possible pathogenic role of nitric oxide (NO). Using a mouse model of mannan-induced Ps and PsA (MIP), where macrophages play a regulatory role by releasing reactive oxygen species (ROS), we found that NO was detectable before disease onset in mice, independent of a functional nicotinamide adenine dinucleotide phosphate oxidase 2 complex. MIP was suppressed by either deletion of Nos2 or inhibition of NO synthases with NG-nitro-l-arginine methyl ester, demonstrating that Nos2-derived NO is pathogenic. NOS2 expression was also up-regulated in lipopolysaccharide- and interferon-γ-stimulated monocyte subsets from patients with PsA compared to healthy controls. Nos2-dependent interleukin-1α (IL-1α) release from skin macrophages was essential for arthritis development by promoting IL-17 production of innate lymphoid cells. We conclude that Nos2-derived NO by tissue macrophages promotes MIP, in contrast to the protective effect by ROS.},
author = {Zhong, Jianghong and Scholz, Tatjana and Yau, Anthony C. Y. and Guerard, Simon and Hüffmeier, Ulrike and Burkhardt, Harald and Holmdahl, Rikard},
doi = {10.1126/sciadv.aas9864},
faupublication = {yes},
journal = {Science Advances},
note = {EVALuna2:34636},
peerreviewed = {Yes},
title = {{Mannan}-induced {Nos2} in macrophages enhances {IL}-17-driven psoriatic arthritis by innate lymphocytes},
volume = {4},
year = {2018}
}
@article{faucris.123177384,
abstract = {Numerous genes are involved in human growth regulation. Recently, autosomal-recessive inherited variants in centrosomal proteins have been identified in Seckel syndrome, primary microcephaly, or microcephalic osteodysplastic primary dwarfism. Common hallmarks of these syndromic forms are severe short stature and microcephaly. In a consanguineous family with two affected children with severe growth retardation and normocephaly, we used homozygosity mapping and next-generation sequencing to identify a homozygous MAP4 variant. MAP4 is a major protein for microtubule assembly during mitosis. High-expression levels in the somite boundaries of zebrafish suggested a role in growth and body segment patterning. The identified variant affects binding sites of kinases necessary for dynamic instability of microtubule formation. We found centrosome amplifications in mitotic fibroblast cells in vivo and in vitro. These numeric centrosomal aberrations were also present during interphase resulting in aberrant ciliogenesis. Furthermore, affected cells showed a dysfunction of the microtubule-dependent assembly of the Golgi apparatus, indicated by a significant lack of compactness of Golgi membranes. These observations demonstrated that MAP4 mutations contribute to the clinical spectrum of centrosomal defects and confirmed the complex role of a centrosomal protein in centrosomal, ciliary, and Golgi regulation associated with severe short stature.},
author = {Zahnleiter, Diana and Hauer, Nadine and Keßler, Kristin and Uebe, Steffen and Sugano, Yuya and Neuhauss, Stephan C. F. and Gießl, Andreas and Ekici, Arif Bülent and Blessing, Holger and Sticht, Heinrich and Dörr, Helmuth-Günther and Reis, André and Thiel, Christian},
doi = {10.1002/humu.22711},
faupublication = {yes},
journal = {Human Mutation},
note = {EVALuna2:9244},
pages = {87-97},
peerreviewed = {Yes},
title = {{MAP4}-dependent regulation of microtubule formation affects centrosome, cilia, and golgi architecture as a central mechanism in growth regulation},
volume = {36},
year = {2015}
}
@article{faucris.117748004,
abstract = {Matrilin-1 is the prototypical member of the matrilin protein family and is highly expressed in cartilage. However, gene targeting of matrilin-1 in mouse did not lead to pronounced phenotypes. Here we used the zebrafish as an alternative model to study matrilin function in vivo. Matrilin-1 displays a multiphasic expression during zebrafish development. In an early phase, with peak expression at about 15 h post-fertilization, matrilin-1 is present throughout the zebrafish embryo with exception of the notochord. Later, when the skeleton develops, matrilin-1 is expressed mainly in cartilage. Morpholino knockdown of matrilin-1 results both in overall growth defects and in disturbances in the formation of the craniofacial cartilage, most prominently loss of collagen II deposition. In fish with mild phenotypes, certain cartilage extracellular matrix components were present, but the tissue did not show features characteristic for cartilage. The cells showed endoplasmic reticulum aberrations but no activation of XBP-1, a marker for endoplasmic reticulum stress. In severe phenotypes nearly all chondrocytes died. During the early expression phase the matrilin-1 knockdown had no effects on cell morphology, but increased cell death was observed. In addition, the broad deposition of collagen II was largely abolished. Interestingly, the early phenotype could be rescued by the co-injection of mRNA coding for the von Willebrand factor C domain of collagen II?1a, indicating that the functional loss of this domain occurs as a consequence of matrilin-1 deficiency. The results show that matrilin-1 is indispensible for zebrafish cartilage formation and plays a role in the early collagen II-dependent developmental events.},
author = {Neacsu, Cristian Dan and Ko, Ya-Ping and Tagariello, Andreas and Karlsen, Kristina Rokenes and Neiss, Wolfram Friedrich and Paulsson, Mats and Wagener, Raimund},
doi = {10.1074/jbc.M113.529933},
faupublication = {yes},
journal = {Journal of Biological Chemistry},
note = {EVALuna2:9239},
pages = {1505-18},
peerreviewed = {Yes},
title = {{Matrilin}-1 is essential for zebrafish development by facilitating collagen {II} secretion},
volume = {289},
year = {2014}
}
@article{faucris.293805654,
abstract = {Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5Brelated neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems.},
author = {Sheppard, Sarah E. and Bryant, Laura and Wickramasekara, Rochelle N. and Vaccaro, Courtney and Robertson, Brynn and Hallgren, Jodi and Hulen, Jason and Watson, Cynthia J. and Faundes, Victor and Duffourd, Yannis and Lee, Pearl and Celeste Simon, M. and de la Cruz, Xavier and Padilla, Natália and Flores-Mendez, Marco and Akizu, Naiara and Smiler, Jacqueline and Da Silva, Renata Pellegrino and Li, Dong and March, Michael and Diaz-Rosado, Abdias and de Barcelos, Isabella Peixoto and Choa, Zhao Xiang and Lim, Chin Yan and Dubourg, Christèle and Journel, Hubert and Demurger, Florence and Mulhern, Maureen and Akman, Cigdem and Lippa, Natalie and Andrews, Marisa and Baldridge, Dustin and Constantino, John and van Haeringen, Arie and Snoeck-Streef, Irina and Chow, Penny and Hing, Anne and Graham, John M. and Au, Margaret and Faivre, Laurence and Shen, Wei and Mao, Rong and Palumbos, Janice and Viskochil, David and Gahl, William and Tifft, Cynthia and Macnamara, Ellen and Hauser, Natalie and Miller, Rebecca and Maffeo, Jessica and Afenjar, Alexandra and Doummar, Diane and Keren, Boris and Arn, Pamela and Macklin-Mantia, Sarah and Meerschaut, Ilse and Callewaert, Bert and Reis, André and Zweier, Christiane and Brewer, Carole and Saggar, Anand and Smeland, Marie F. and Kumar, Ajith and Elmslie, Frances and Deshpande, Charu and Nizon, Mathilde and Cogne, Benjamin and van Ierland, Yvette and Wilke, Martina and van Slegtenhorst, Marjon and Koudijs, Suzanne and Chen, Jin Yun and Dredge, David and Pier, Danielle and Wortmann, Saskia and Kamsteeg, Erik Jan and Koch, Johannes and Haynes, Devon and Pollack, Lynda and Titheradge, Hannah and Ranguin, Kara and Denommé-Pichon, Anne Sophie and Weber, Sacha and de la Fuente, Rubén Pérez and del Pozo, Jaime Sánchez and Rosales, Jose Miguel Lezana and Joset, Pascal and Steindl, Katharina and Rauch, Anita and Mei, Davide and Mari, Francesco and Guerrini, Renzo and Lespinasse, James and Mau-Them, Frédéric Tran and Philippe, Christophe and Dauriat, Benjamin and Raymond, Laure and Moutton, Sébastien and Cueto-González, Anna M. and Tan, Tiong Yang and Mignot, Cyril and Grotto, Sarah and Renaldo, Florence and Drivas, Theodore G. and Hennessy, Laura and Raper, Anna and Parenti, Ilaria and Kaiser, Frank J. and Kuechler, Alma and Busk, Øyvind L. and Islam, Lily and Siedlik, Jacob A. and Henderson, Lindsay B. and Juusola, Jane and Person, Richard and Schnur, Rhonda E. and Vitobello, Antonio and Banka, Siddharth and Bhoj, Elizabeth J. and Stessman, Holly A.F.},
doi = {10.1126/sciadv.ade1463},
faupublication = {yes},
journal = {Science Advances},
note = {CRIS-Team Scopus Importer:2023-03-24},
peerreviewed = {Yes},
title = {{Mechanism} of {KMT5B} haploinsufficiency in neurodevelopment in humans and mice},
volume = {9},
year = {2023}
}
@article{faucris.213163761,
abstract = {Many genetic neurological disorders exhibit variable expression within affected families, often exemplified by variations in disease age at onset. Epistatic effects (i.e. effects of modifier genes on the disease gene) may underlie this variation, but the mechanistic basis for such epistatic interactions is rarely understood. Here we report a novel epistatic interaction between SPAST and the contiguous gene DPY30, which modifies age at onset in hereditary spastic paraplegia, a genetic axonopathy. We found that patients with hereditary spastic paraplegia caused by genomic deletions of SPAST that extended into DPY30 had a significantly younger age at onset. We show that, like spastin, the protein encoded by SPAST, the DPY30 protein controls endosomal tubule fission, traffic of mannose 6-phosphate receptors from endosomes to the Golgi, and lysosomal ultrastructural morphology. We propose that additive effects on this pathway explain the reduced age at onset of hereditary spastic paraplegia in patients who are haploinsufficient for both genes.},
author = {Newton, Timothy and Allison, Rachel and Edgar, James R. and Lumb, Jennifer H. and Rodger, Catherine E. and Manna, Paul T. and Rizo, Tania and Kohl, Zacharias and Nygren, Anders O. H. and Arning, Larissa and Schuele, Rebecca and Depienne, Christel and Goldberg, Lisa and Frahm, Christiane and Stevanin, Giovanni and Durr, Alexandra and Schoels, Ludger and Winner, Beate and Beetz, Christian and Reid, Evan},
doi = {10.1093/brain/awy034},
faupublication = {yes},
journal = {Brain},
note = {EVALuna2:35784},
pages = {1286-1299},
peerreviewed = {Yes},
title = {{Mechanistic} basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia},
volume = {141},
year = {2018}
}
@article{faucris.241522723,
abstract = {Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10−8) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.},
author = {Kho, Pik Fang and Amant, Frederic and Annibali, Daniela and Ashton, Katie and Attia, John and Auer, Paul L. and Beckmann, Matthias and Black, Amanda and Brinton, Louise and Buchanan, Daniel D. and Chanock, Stephen J. and Chen, Chu and Chen, Maxine M. and Cheng, Timothy H.T. and Cook, Linda S. and Crous-Bous, Marta and Czene, Kamila and De Vivo, Immaculata and Dennis, Joe and Dörk, Thilo and Dowdy, Sean C. and Dunning, Alison M. and Dürst, Matthias and Easton, Douglas F. and Ekici, Arif Bülent and Fasching, Peter and Fridley, Brooke L. and Friedenreich, Christine M. and García-Closas, Montserrat and Gaudet, Mia M. and Giles, Graham G. and Goode, Ellen L. and Gorman, Maggie and Haiman, Christopher A. and Hall, Per and Hankinson, Susan E. and Hein, Alexander and Hillemanns, Peter and Hodgson, Shirley and Hoivik, Erling A. and Holliday, Elizabeth G. and Hunter, David J. and Jones, Angela and Kraft, Peter and Krakstad, Camilla and Lambrechts, Diether and Le Marchand, Loic and Liang, Xiaolin and Lindblom, Annika and Lissowska, Jolanta and Long, Jirong and Lu, Lingeng and Magliocco, Anthony M. and Martin, Lynn and McEvoy, Mark and Milne, Roger L. and Mints, Miriam and Nassir, Rami and Otton, Geoffrey and Palles, Claire and Pooler, Loreall and Proietto, Tony and Rebbeck, Timothy R. and Renner, Stefan and Risch, Harvey A. and Rübner, Matthias and Runnebaum, Ingo and Sacerdote, Carlotta and Sarto, Gloria E. and Schumacher, Fredrick and Scott, Rodney J. and Setiawan, V. Wendy and Shah, Mitul and Sheng, Xin and Shu, Xiao Ou and Southey, Melissa C. and Tham, Emma and Tomlinson, Ian and Trovik, Jone and Turman, Constance and Tyrer, Jonathan P. and Van Den Berg, David and Wang, Zhaoming and Wentzensen, Nicolas and Xia, Lucy and Xiang, Yong Bing and Yang, Hannah P. and Yu, Herbert and Zheng, Wei and Webb, Penelope M. and Thompson, Deborah J. and Spurdle, Amanda B. and Glubb, Dylan M. and O'Mara, Tracy A.},
doi = {10.1002/ijc.33206},
faupublication = {yes},
journal = {International Journal of Cancer},
keywords = {endometrial cancer risk; HDL cholesterol; LDL cholesterol; Mendelian randomization; triglycerides},
note = {CRIS-Team Scopus Importer:2020-08-14},
peerreviewed = {Yes},
title = {{Mendelian} randomization analyses suggest a role for cholesterol in the development of endometrial cancer},
year = {2020}
}
@inproceedings{faucris.274481705,
address = {LONDON},
author = {Rieger, Melissa and Moutton, Sebastien and Verheyen, Sarah and Speicher, Michael and Leheup, Bruno and Bonnet, Celine and Steindl, Katharina and Boneda, Beatrice and Rauch, Anita and Krumbiegel, Mandy and Reis, André and Hüffmeier, Ulrike},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
doi = {10.1016/j.ejmg.2022.104669},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2022-05-06},
pages = {245-246},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Microdeletions} at 19p13.11 in four individuals with neurodevelopmental delay},
year = {2022}
}
@article{faucris.286620047,
abstract = {Only few copy number variants at chromosome 19p13.11 have been reported, thus associated clinical information is scarce. Proximal to these copy number losses, we now identified deletions in five unrelated individuals with neurodevelopmental disorders. They presented with psychomotor delay as well as behavioral and sleeping disorders, while complex cardiovascular, skeletal, and various other malformations were more variable. Dysmorphic features were rather unspecific and not considered as a recognizable gestalt. Neither of the analyzed parents carried their offsprings' deletions, indicating de novo occurrence. The deletion sizes ranged between 0.7 and 5.2 Mb, were located between 18 and 24 megabases from the telomere, and contained a variable number of protein-coding genes (n = 25–68). Although not all microdeletions shared a common region, the smallest common overlap of some of the deletions provided interesting insights in the chromosomal region 19p13.11p12. Diligent literature review using OMIM and Pubmed did not identify a satisfying candidate gene for neurodevelopmental disorders. In the literature, a de novo in-frame deletion in MAU2 was considered pathogenic in an individual with Cornelia de Lange syndrome. Therefore, the clinical differential diagnosis of this latter syndrome in one individual and the encompassment of MAU2 in three individuals' deletions suggest clinical and genetic overlap with this specific syndrome. Three of the four here reported individuals with deletion encompassing GDF1 had different congenital heart defects, suggesting that this gene's haploinsufficiency might contribute to the cardiovascular phenotype, however, with reduced penetrance. Our findings indicate an association of microdeletions at 19p13.11/ 19p13.11p12 with neurodevelopmental disorders, variable symptoms, and malformations, and delineate the phenotypic spectrum of deletions within this genomic region.},
author = {Rieger, Melissa and Moutton, Sébastien and Verheyen, Sarah and Steindl, Katharina and Popp, Bernt and Leheup, Bruno and Bonnet, Céline and Oneda, Beatrice and Rauch, Anita and Reis, André and Krumbiegel, Mandy and Hüffmeier, Ulrike},
doi = {10.1016/j.ejmg.2022.104669},
faupublication = {yes},
journal = {European Journal of Medical Genetics},
keywords = {19p13.11p12; Deletion; GDF1; Malformation; MAU2; NDD},
month = {Jan},
note = {CRIS-Team Scopus Importer:2022-12-16},
peerreviewed = {Yes},
title = {{Microdeletions} at 19p13.11p12 in five individuals with neurodevelopmental delay},
volume = {66},
year = {2023}
}
@article{faucris.208513499,
abstract = {Mutations in BCOR cause X-linked dominant and X-linked recessive forms of syndromic microphthalmia. By exome sequencing, we identified the recurrent BCOR mutation p.Pro85Leu in two brothers and their unaffected mother. While the older brother's phenotype completely fits the described phenotypic spectrum of X-linked recessive BCOR-associated Lenz microphthalmia syndrome, the younger brother showed developmental delay, microcephaly, and skeletal anomalies, but not the key feature of microphthalmia. In contrast to the previously published families, our findings demonstrate a large variability of BCOR-associated, syndromic phenotypes, indicating incomplete penetrance of p.Pro85Leu with regards to microphthalmia in males.
},
author = {Kraus, Cornelia and Uebe, Steffen and Thiel, Christian and Ekici, Arif Bülent and Reis, André and Zweier, Christiane},
doi = {10.1002/ajmg.a.40640},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
note = {EVALuna2:34843},
peerreviewed = {Yes},
title = {{Microphthalmia} is not a mandatory finding in {X}-linked recessive syndromic microphthalmia caused by the recurrent {BCOR} variant p.{Pro85Leu}},
year = {2018}
}
@inproceedings{faucris.242418905,
address = {ROCKVILLE},
author = {Karg, Margarete and John, Lukas and Refaian, Narin and Büttner, Christian and Rottmar, Tanja and Sommer, Jonas and Bock, Barbara and Resheq, Yazid and Ksander, Bruce and Heindl, Ludwig M. and Mackensen, Andreas and Bosch, Jacobus},
booktitle = {INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE},
date = {2020-05-01/2020-05-07},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2020-09-11},
peerreviewed = {unknown},
publisher = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
title = {{Midkine} is a tumor cell survival factor that displays metastatic and therapeutic resistance functions in uveal melanoma},
venue = {ONLINE},
year = {2020}
}
@article{faucris.279766189,
abstract = {Uveal melanoma is a rare form of melanoma that originates in the eye, exerts widespread therapeutic resistance, and displays an inherent propensity for hepatic metastases. Because metastatic disease is characterized by poor survival, there is an unmet clinical need to identify new therapeutic targets in uveal melanoma. Here, we show that the pleiotropic cytokine midkine is expressed in uveal melanoma. Midkine expression in primary uveal melanoma significantly correlates with poor survival and is elevated in patients that develop metastatic disease. Monosomy 3 and histopathologic staging parameters are associated with midkine expression. In addition, we demonstrate that midkine promotes survival, migration across a barrier of hepatic sinusoid endothelial cells and resistance to AKT/mTOR inhibition. Furthermore, midkine is secreted and mediates mTOR activation by maintaining phosphorylation of the mTOR target RPS6 in uveal melanoma cells. Therefore, midkine is identified as a uveal melanoma cell survival factor that drives metastasis and therapeutic resistance, and could be exploited as a biomarker as well as a new therapeutic target.
IMPLICATIONS: Midkine is identified as a survival factor that drives liver metastasis and therapeutic resistance in melanoma of the eye.},
author = {Karg, Margarete and John, Lukas and Refaian, Nasrin and Büttner, Christian and Rottmar, Tanja and Sommer, Jonas and Bock, Barbara and Resheq, Yazid and Ksander, Bruce R. and Heindl, Ludwig M. and Mackensen, Andreas and Bosch, Jacobus J.},
doi = {10.1158/1541-7786.MCR-20-0692},
faupublication = {yes},
journal = {Molecular Cancer Research},
note = {EVALuna2:503899},
pages = {1320-1336},
peerreviewed = {Yes},
title = {{Midkine} {Promotes} {Metastasis} and {Therapeutic} {Resistance} via {mTOR}/{RPS6} in {Uveal} {Melanoma}.},
volume = {20},
year = {2022}
}
@inproceedings{faucris.242414665,
address = {ROCKVILLE},
author = {Matthaei, Mario and Clahsen, Thomas and Büttner, Christian and Ekici, Arif Bülent and Siebelmann, Sebastian and Heindl, Ludwig M. and Bachmann, Bjoern and Cursiefen, Claus and Hribek, Agathe},
booktitle = {INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE},
date = {2020-05-01/2020-05-07},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2020-09-11},
peerreviewed = {unknown},
publisher = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
title = {{MiR}-29 related deposition of extracellular matrix in {Fuchs} endothelial corneal dystrophy},
venue = {ONLINE},
year = {2020}
}
@article{faucris.205285922,
abstract = {Although the role of typical Rho GTPases and other Rho-linked proteins in synaptic plasticity and cognitive function and dysfunction is widely acknowledged, the role of atypical Rho GTPases (such as RHOBTB2) in neurodevelopment has barely been characterized. We have now identified de novo missense variants clustering in the BTB-domain-encoding region of RHOBTB2 in ten individuals with a similar phenotype, including early-onset epilepsy, severe intellectual disability, postnatal microcephaly, and movement disorders. Three of the variants were recurrent. Upon transfection of HEK293 cells, we found that mutant RHOBTB2 was more abundant than the wild-type, most likely because of impaired degradation in the proteasome. Similarly, elevated amounts of the Drosophila ortholog RhoBTB in vivo were associated with seizure susceptibility and severe locomotor defects. Knockdown of RhoBTB in the Drosophila dendritic arborization neurons resulted in a decreased number of dendrites, thus suggesting a role of RhoBTB in dendritic development. We have established missense variants in the BTB-domain-encoding region of RHOBTB2 as causative for a developmental and epileptic encephalopathy and have elucidated the role of atypical Rho GTPase RhoBTB in Drosophila neurological function and possibly dendrite development.
},
author = {Straub, Jonas and Konrad, Enrico and Grüner, Johanna and Toutain, Annick and Bok, Levinus A. and Cho, Megan T. and Crawford, Heather P. and Dubbs, Holly and Douglas, Ganka and Jobling, Rebekah and Johnson, Diana and Krock, Bryan and Mikati, Mohamad A. and Nesbitt, Addie and Nicolai, Joost and Phillips, Meredith and Poduri, Annapurna and Ortiz-Gonzalez, Xilma R. and Powis, Zoe and Santani, Avni and Smith, Lacey and Stegmann, Alexander P. A. and Stumpel, Constance and Vreeburg, Maaike and Fliedner, Anna and Gregor, Anne and Sticht, Heinrich and Zweier, Christiane},
doi = {10.1016/j.ajhg.2017.11.008},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:33715},
pages = {44-57},
peerreviewed = {Yes},
title = {{Missense} {Variants} in {RHOBTB2} {Cause} a {Developmental} and {Epileptic} {Encephalopathy} in {Humans}, and {Altered} {Levels} {Cause} {Neurological} {Defects} in {Drosophila}},
volume = {102},
year = {2018}
}
@article{faucris.221623298,
abstract = {Damage of mitochondrial DNA (mtDNA) with reduction in copy number has been proposed as a biomarker for mitochondrial dysfunction and oxidative stress. Chronic kidney disease (CKD) is associated with increased mortality and risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. Here we investigated the prognostic role of mtDNA copy number for cause-specific mortality in 4812 patients from the German Chronic Kidney Disease study, an ongoing prospective observational national cohort study of patients with CKD stage G3 and A1-3 or G1-2 with overt proteinuria (A3) at enrollment. MtDNA was quantified in whole blood using a plasmid-normalized PCR-based assay. At baseline, 1235 patients had prevalent cardiovascular disease. These patients had a significantly lower mtDNA copy number than patients without cardiovascular disease (fully-adjusted model: odds ratio 1.03, 95% confidence interval [CI] 1.01-1.05 per 10 mtDNA copies decrease). After four years of follow-up, we observed a significant inverse association between mtDNA copy number and all-cause mortality, adjusted for kidney function and cardiovascular disease risk factors (hazard ratio 1.37, 95% CI 1.09-1.73 for quartile 1 compared to quartiles 2-4). When grouped by causes of death, estimates pointed in the same direction for all causes but in a fully-adjusted model decreased copy numbers were significantly lower only in infection-related death (hazard ratio 1.82, 95% CI 1.08-3.08). A similar association was observed for hospitalizations due to infections in 644 patients (hazard ratio 1.19, 95% CI 1.00-1.42 in the fully-adjusted model). Thus, our data support a role of mitochondrial dysfunction in increased cardiovascular disease and mortality risks as well as susceptibility to infections in patients with CKD.},
author = {Fazzini, Federica and Lamina, Claudia and Fendt, Liane and Schultheiss, Ulla T. and Kotsis, Fruzsina and Hicks, Andrew A. and Meiselbach, Heike and Weissensteiner, Hansi and Forer, Lukas and Krane, Vera and Eckardt, Kai-Uwe and Köttgen, Anna and Kronenberg, Florian and Schneider, Markus and Dienemann, Thomas and Prokosch, Hans-Ulrich and Bärthlein, Barbara and Beck, Andreas and Ganslandt, Thomas and Reis, André and Ekici, Arif Bülent and Avendaño, Susanne and Becker-Grosspitsch, Dinah and Alberth-Schmidt, Ulrike and Hausknecht, Birgit and Zitzmann, Rita and Weigel, Anke and Walz, Gerd and Schultheiß, Ulla and Meder, Simone and Mitsch, Erna and Reinhard, Ursula and Floege, Jürgen and Schlieper, Georg and Saritas, Turgay and Ernst, Sabine and Beaujean, Nicole and Schaeffner, Elke and Baid-Agrawal, Seema and Theisen, Kerstin and Haller, Hermann and Menne, Jan and Zeier, Martin and Sommerer, Claudia and Woitke, Rebecca and Wolf, Gunter and Busch, Martin and Fuß, Rainer and Sitter, Thomas and Blank, Claudia and Wanner, Christoph and Börner-Klein, Antje and Bauer, Britta and Raschenberger, Julia and Kollerits, Barbara and Schönherr, Sebastian and Oefner, Peter and Gronwald, Wolfram and Zacharias, Helena and Schmid, Matthias and Nadal, Jennifer},
doi = {10.1016/j.kint.2019.04.021},
faupublication = {yes},
journal = {Kidney International},
keywords = {chronic kidney disease; infections; mitochondrial DNA copy number; mortality},
note = {CRIS-Team Scopus Importer:2019-07-02},
peerreviewed = {Yes},
title = {{Mitochondrial} {DNA} copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease},
year = {2019}
}
@article{faucris.252782257,
abstract = {models of PD, focusing on those phenotypes that have been detected in genetic and sporadic PD models. An additional point covered in this review will be the use of induced pluripotent stem cell (iPSC)-derived technologies to model cell-cell interactions in PD.},
author = {Rizo Garza, Tania and Simmnacher, Katrin and Lanfer, Jonas and Rizo, Tania and Kaindl, Johanna and Winner, Beate},
doi = {10.3389/fncel.2019.00571},
faupublication = {yes},
journal = {Frontiers in Cellular Neuroscience},
pages = {571},
peerreviewed = {Yes},
title = {{Modeling} {Cell}-{Cell} {Interactions} in {Parkinson}'s {Disease} {Using} {Human} {Stem} {Cell}-{Based} {Models}.},
volume = {13},
year = {2019}
}
@article{faucris.234238095,
abstract = {Parkinson’s disease (PD) is the most frequently occurring movement disorder, with an increasing incidence due to an aging population. For many years, the post-mortem brain was regarded as the gold standard for the analysis of the human pathology of this disease. However, modern stem cell technologies, including the analysis of patient-specific neurons and glial cells, have opened up new avenues for dissecting the pathologic mechanisms of PD. Most data on morphological changes, such as cell death or changes in neurite complexity, or functional deficits were acquired in 2D and few in 3D models. This review will examine the prerequisites for human disease modeling in PD, covering the generation of midbrain neurons, 3D organoid midbrain models, the selection of controls including genetically engineered lines, and the study of cell-cell interactions. We will present major disease phenotypes in human in vitro models of PD, focusing on those phenotypes that have been detected in genetic and sporadic PD models. An additional point covered in this review will be the use of induced pluripotent stem cell (iPSC)-derived technologies to model cell-cell interactions in PD.},
author = {Simmnacher, Katrin and Lanfer, Jonas and Rizo, Tania and Kaindl, Johanna and Winner, Beate},
doi = {10.3389/fncel.2019.00571},
faupublication = {yes},
journal = {Frontiers in Cellular Neuroscience},
keywords = {disease modeling; dopaminergic neuron; glia; inflammation; iPSC; neurodegeneration; organoid; Parkinson’s disease},
month = {Jan},
note = {CRIS-Team Scopus Importer:2020-02-14},
peerreviewed = {Yes},
title = {{Modeling} {Cell}-{Cell} {Interactions} in {Parkinson}’s {Disease} {Using} {Human} {Stem} {Cell}-{Based} {Models}},
volume = {13},
year = {2020}
}
@article{faucris.120786204,
author = {Schulze, Markus and Hoja, Sabine and Winner, Beate and Winkler, Jürgen and Edenhofer, Frank and Riemenschneider, Markus J.},
doi = {10.1089/scd.2015.0266},
faupublication = {yes},
journal = {Stem Cells and Development},
note = {EVALuna2:26227},
pages = {569-71},
peerreviewed = {Yes},
title = {{Model} {Testing} of {PluriTest} with {Next}-{Generation} {Sequencing} {Data}},
volume = {25},
year = {2016}
}
@article{faucris.232909979,
abstract = {In light of the organ shortage, there is a great responsibility to assess postmortal organs for which procurement has been consented and to increase the life span of transplanted organs. The former responsibility has moved many centers to accept extended criteria organs. The latter responsibility requires an exact diagnosis and, if possible, omission of the harmful influence on the transplant. We report the course of a kidney transplant that showed a steady decline of function over a decade, displaying numerous cysts of different sizes. Clinical workup excluded the most frequent causes of chronic transplant failure. The filed allocation documents mentioned the donor's disease of oral-facial-digital syndrome, a rare ciliopathy, which can also affect the kidney. Molecular diagnosis was performed by culturing donor tubular cells from the recipient ' s urine more than 10 years after transplantation. Next-generation panel sequencing with DNA from tubular urinary cells revealed a novel truncating mutation in OFD1, which sufficiently explains the features of the kidney transplants, also found in the second kidney allograft. Despite this severe donor disease, lifesaving transplantation with good long-term outcome was enabled for 5 recipients.},
author = {Wiesener, Antje and Knaup, Karl and Büttner-Herold, Maike and Dieterle, Anne and Stoeckert, Johanna and Riedl, Bernhard and Morath, Christian and Wald, Alexandra and Vondran, Florian and Braun, Felix and Schoedel, Johannes and Schüler, Markus and Schiffer, Mario and Amann, Kerstin Ute and Reis, André and Kraus, Cornelia and Wiesener, Michael S.},
doi = {10.1111/ajt.15738},
faupublication = {yes},
journal = {American Journal of Transplantation},
month = {Jan},
note = {CRIS-Team WoS Importer:2020-01-31},
peerreviewed = {Yes},
title = {{Molecular} diagnosis of kidney transplant failure based on urine},
year = {2020}
}
@inproceedings{faucris.228457773,
address = {HOBOKEN},
author = {Knaup, Karl and Wiesener, A. and Buettner-Herold, M. and Dieterle, A. and Morath, C. and Vondran, F. W. R. and Wald, A. and Braun, F. and Schüler, Markus and Schoedel, J. and Schiffer, Mario and Reis, André and Amann, Kerstin Ute and Wiesener, M. S.},
booktitle = {TRANSPLANT INTERNATIONAL},
doi = {10.1111/ajt.15738},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-29},
pages = {34-34},
peerreviewed = {unknown},
publisher = {WILEY},
title = {{MOLECULAR} {DIAGNOSIS} {OF} {KIDNEY} {TRANSPLANT} {FAILURE} {BY} {THE} {URINE}},
year = {2019}
}
@article{faucris.271010269,
abstract = {Background: Patients with atrial fibrillation have a relevant risk for ischemic stroke despite the recommended use of direct oral anticoagulants (DOAC). The risk correlates with the functional DOAC plasma levels in clinical trials, but the value of their measurement in community use remains undetermined. Objectives: We aim to investigate the clinical implications and the prognostic value of DOAC plasma level measurement during steady state. Methods: In this observational clinical cohort study among patients with ischemic stroke and atrial fibrillation, 397 individuals on oral anticoagulants for secondary stroke prevention were included between 2016 and 2020. The functional DOAC plasma levels were measured during steady state. Early stroke recurrence within 3 months was recorded as the main outcome parameter. Results: Three hundred ninety-seven patients (201 female, mean age 78 [±9] years, median CHA2DS2VASc-Score 6 [interquartile range 5–7]) were included. Mean DOAC plasma trough level was 95.9 (±66.9) ng/ml. A high glomerular filtration rate (GFR) was an independent predictor of lower levels in a multivariate model (R coefficient: −0.174, P =.014). During follow-up, 10 patients (3%) suffered from early ischemic stroke recurrence despite the use of DOAC, while 10 clinically relevant bleeding complications occurred (3%). Ischemic stroke recurrence was associated with numerical lower plasma levels for patients on apixaban and dabigatran after propensity score matching. Conclusions: Monitoring of DOAC plasma levels could help to identify patients with increased risk for stroke recurrence and should be considered for certain subgroups, including patients with high GFR.},
author = {Siedler, Gabriela and Macha, Kosmas and Stoll, Svenja and Plechschmidt, Johannes and Wang, Ruihao and Gerner, Stefan and Strasser, Erwin and Schwab, Stefan and Kallmünzer, Bernd},
doi = {10.1111/jth.15677},
faupublication = {yes},
journal = {Journal of Thrombosis and Haemostasis},
keywords = {atrial fibrillation; cardioembolic stroke; direct oral anticoagulants; ischemic stroke; secondary prevention},
note = {CRIS-Team Scopus Importer:2022-03-18},
peerreviewed = {Yes},
title = {{Monitoring} of direct oral anticoagulants plasma levels for secondary stroke prevention},
year = {2022}
}
@inproceedings{faucris.248096779,
address = {LONDON},
author = {Thiel, C. T. and Hauer, Nadine and Vogl, C. and Uebe, Steffen and Sticht, Heinrich and Ekici, Arif Bülent and Kraus, Cornelia and Dörr, Helmuth-Günther and Reis, André},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {240-240},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Mono}-allelic deleterious variants in autosomal recessive skeletal dysplasia genes are strongly associated with idiopathic short stature},
year = {2020}
}
@article{faucris.216825354,
abstract = {Purpose: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5–6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease. Methods: Exome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. A heterozygous Ramp2 knockout mouse model was generated for in vivo functional study. Results: Using exome sequencing analysis and replication studies, we identified pathogenic variants in receptor activity-modifying protein 2 (RAMP2) within three genetically diverse populations (Han Chinese, German, and Indian). Six heterozygous RAMP2 pathogenic variants (Glu39Asp, Glu54Lys, Phe103Ser, Asn113Lysfs*10, Glu143Lys, and Ser171Arg) were identified among 16 of 4763 POAG patients, whereas no variants were detected in any exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s aggregated in transfected cells and resulted in damage to the AM-RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 allele led to cAMP reduction and retinal ganglion cell death in mice. Conclusion: This study demonstrated that disruption of RAMP2/CRLR-cAMP axis could cause POAG and identified a potential therapeutic intervention for POAG.},
author = {Gong, Bo and Zhang, Houbin and Huang, Lulin and Chen, Yuhong and Shi, Yi and Tam, Pancy Oi Sin and Zhu, Xianjun and Huang, Yi and Lei, Bo and Sundaresan, Periasamy and Li, Xi and Jiang, Linxin and Yang, Jialiang and Lin, Ying and Lu, Fang and Chen, Lijia and Li, Yuanfeng and Leung, Christopher Kai Shun and Guo, Xiaoxin and Zhang, Shanshan and Huang, Guo and Wu, Yaqi and Zhou, Tongdan and Shuai, Ping and Tham, Clement Chee Yung and Weisschuh, Nicole and Krishnadas, Subbaiah Ramasamy and Mardin, Christian Y. and Reis, André and Yang, Jiyun and Zhang, Lin and Zhou, Yu and Wang, Ziyan and Qu, Chao and Shaw, Peter X. and Pang, Chi Pui and Sun, Xinghuai and Zhu, Weiquan and Li, Dean Yaw and Pasutto, Francesca and Yang, Zhenglin},
doi = {10.1038/s41436-019-0507-0},
faupublication = {yes},
journal = {Genetics in Medicine},
keywords = {exome sequencing; heterozygous pathogenic variant; primary open-angle glaucoma (POAG); receptor activity-modifying protein 2 (RAMP2); retinal ganglion cell (RGC)},
note = {CRIS-Team Scopus Importer:2019-05-02},
peerreviewed = {Yes},
title = {{Mutant} {RAMP2} causes primary open-angle glaucoma via the {CRLR}-{cAMP} axis},
year = {2019}
}
@article{faucris.122449624,
abstract = {Recently, we identified in two individuals with intellectual disability (ID) different de novo mutations in DEAF1, which encodes a transcription factor with an important role in embryonic development. To ascertain whether these mutations in DEAF1 are causative for the ID phenotype, we performed targeted resequencing of DEAF1 in an additional cohort of over 2,300 individuals with unexplained ID and identified two additional individuals with de novo mutations in this gene. All four individuals had severe ID with severely affected speech development, and three showed severe behavioral problems. DEAF1 is highly expressed in the CNS, especially during early embryonic development. All four mutations were missense mutations affecting the SAND domain of DEAF1. Altered DEAF1 harboring any of the four amino acid changes showed impaired transcriptional regulation of the DEAF1 promoter. Moreover, behavioral studies in mice with a conditional knockout of Deaf1 in the brain showed memory deficits and increased anxiety-like behavior. Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1.},
author = {Vulto-Van Silfhout, Anneke T. and Rajamanickam, Shivakumar and Jensik, Philip J. and Vergult, Sarah and De Rocker, Nina and Newhall, Kathryn J. and Raghavan, Ramya and Reardon, Sara N. and Jarrett, Kelsey and Mcintyre, Tara and Bulinski, Joseph and Ownby, Stacy L. and Huggenvik, Jodi I. and Mcknight, G. Stanley and Rose, Gregory M. and Cai, Xiang and Willaert, Andy and Zweier, Christiane and Endele, Sabine and De Ligt, Joep and Van Bon, Bregje W. M. and Lugtenberg, Dorien and De Vries, Petra F. and Veltman, Joris A. and Van Bokhoven, Hans and Brunner, Han G. and Rauch, Anita and De Brouwer, Arjan P. M. and Carvill, Gemma L. and Hoischen, Alexander and Mefford, Heather C. and Eichler, Evan E. and Vissers, Lisenka E. L. M. and Menten, Bjorn and Collard, Michael W. and De Vries, Bert B. A.},
doi = {10.1016/j.ajhg.2014.03.013},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9219},
pages = {649-61},
peerreviewed = {Yes},
title = {{Mutations} affecting the {SAND} domain of {DEAF1} cause intellectual disability with severe speech impairment and behavioral problems},
volume = {94},
year = {2014}
}
@article{faucris.259566174,
abstract = {PURPOSE: Among patients with metastatic breast cancer (mBC), the frequency of germline mutations in cancer susceptibility genes and the clinical relevance of these mutations are unclear. In this study, a prospective cohort of patients with mBC was used to determine mutation rates for breast cancer (BC) predisposition genes, to evaluate the clinical characteristics of patients with mutations, and to assess the influence of mutations on patient outcome. PATIENTS AND METHODS: Germline DNA from 2,595 patients with mBC enrolled in the prospective PRAEGNANT registry was evaluated for mutations in cancer predisposition genes. The frequencies of mutations in known BC predisposition genes were compared with results from a prospective registry of patients with nonmetastatic BC sequenced using the same QIAseq method and with public reference controls. Associations between mutation status and tumor characteristics, progression-free survival, and overall survival were assessed. RESULTS: Germline mutations in 12 established BC predisposition genes (including BRCA1 and BRCA2) were detected in 271 (10.4%) patients. A mutation in BRCA1 or BRCA2 was seen in 129 patients (5.0%). BRCA1 mutation carriers had a higher proportion of brain metastasis (27.1%) compared with nonmutation carriers (12.8%). Mutations were significantly enriched in PRAEGNANT patients with mBC compared with patients with nonmetastatic BC (10.4% v 6.6%, P < .01). Mutations did not significantly modify progression-free survival or overall survival for patients with mBC. CONCLUSION: Multigene panel testing may be considered in all patients with mBC because of the high frequency of germline mutations in BRCA1/2 and other BC predisposition genes. Although the prognosis of mutation carriers and nonmutation carriers with mBC was similar, differences observed in tumor characteristics have implications for treatment and for future studies of targeted therapies.},
author = {Fasching, Peter and Yadav, Siddhartha and Hu, Chunling and Wunderle, Marius and Häberle, Lothar and Hart, Steven N. and Rübner, Matthias and Polley, Eric C. and Lee, Kun Y. and Gnanaolivu, Rohan D. and Hadji, Peyman and Hübner, Hanna and Tesch, Hans and Ettl, Johannes and Overkamp, Friedrich and Lux, Michael P. and Ekici, Arif Bülent and Volz, Bernhard and Uhrig, Sabrina and Lüftner, Diana and Wallwiener, Markus and Müller, Volkmar and Belleville, Erik and Untch, Michael and Kolberg, Hans Christian and Beckmann, Matthias and Reis, André and Hartmann, Arndt and Janni, Wolfgang and Wimberger, Pauline and Taran, Florin Andrei and Fehm, Tanja N. and Wallwiener, Diethelm and Brucker, Sara Y. and Schneeweiss, Andreas and Hartkopf, Andreas D. and Couch, Fergus J.},
doi = {10.1200/JCO.20.01200},
faupublication = {yes},
journal = {Journal of Clinical Oncology},
note = {CRIS-Team Scopus Importer:2021-06-04},
pages = {1619-1630},
peerreviewed = {Yes},
title = {{Mutations} in {BRCA1}/2 and {Other} {Panel} {Genes} in {Patients} {With} {Metastatic} {Breast} {Cancer} -{Association} {With} {Patient} and {Disease} {Characteristics} and {Effect} on {Prognosis}},
volume = {39},
year = {2021}
}
@article{faucris.123877864,
abstract = {There are two known mRNA degradation pathways, 3' to 5' and 5' to 3'. We identified likely pathogenic variants in two genes involved in these two pathways in individuals with intellectual disability. In a large family with multiple branches, we identified biallelic variants in DCPS in three affected individuals; a splice site variant (c.636+1G>A) that results in an in-frame insertion of 45 nucleotides and a missense variant (c.947C>T; p.Thr316Met). DCPS decaps the cap structure generated by 3' to 5' exonucleolytic degradation of mRNA. In vitro decapping assays showed an ablation of decapping function for both variants in DCPS. In another family, we identified a homozygous mutation (c.161T>C; p.Phe54Ser) in EDC3 in two affected children. EDC3 stimulates DCP2, which decaps mRNAs at the beginning of the 5' to 3' degradation pathway. In vitro decapping assays showed that altered EDC3 is unable to enhance DCP2 decapping at low concentrations and even inhibits DCP2 decapping at high concentration. We show that individuals with biallelic mutations in these genes of seemingly central functions are viable and that these possibly lead to impairment of neurological functions linking mRNA decapping to normal cognition. Our results further affirm an emerging theme linking aberrant mRNA metabolism to neurological defects.},
author = {Ahmed, Iltaf and Buchert, Rebecca and Zhou, Mi and Jiao, Xinfu and Mittal, Kirti and Sheikh, Taimoor I. and Scheller, Ute and Vasli, Nasim and Rafiq, Muhammad Arshad and Brohi, M. Qasim and Mikhailov, Anna and Ayaz, Muhammad and Bhatti, Attya and Sticht, Heinrich and Nasr, Tanveer and Carter, Melissa T. and Uebe, Steffen and Reis, André and Ayub, Muhammad and John, Peter and Kiledjian, Megerditch and Vincent, John B. and Jamra, Rami Abou},
doi = {10.1093/hmg/ddv069},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:9274},
pages = {3172-80},
peerreviewed = {Yes},
title = {{Mutations} in {DCPS} and {EDC3} in autosomal recessive intellectual disability indicate a crucial role for {mRNA} decapping in neurodevelopment},
volume = {24},
year = {2015}
}
@article{faucris.119559264,
author = {Koerber, Andreas and Moessner, Rotraut and Renner, Regina and Sticht, Heinrich and Wilsmann-Theis, Dagmar and Schulz, Peter and Sticherling, Michael and Traupe, Heiko and Hüffmeier, Ulrike},
doi = {10.1038/jid.2013.214},
faupublication = {yes},
journal = {Journal of Investigative Dermatology},
note = {EVALuna2:9180},
pages = {2634-7},
peerreviewed = {Yes},
title = {{Mutations} in {IL36RN} in patients with generalized pustular psoriasis},
volume = {133},
year = {2013}
}
@article{faucris.283588785,
abstract = {Galloway-Mowat syndrome (GAMOS) is an autosomalrecessive disease characterized by the combination of earlyonset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.},
author = {Braun, Daniela A. and Rao, Jia and Mollet, Geraldine and Schapiro, David and Daugeron, Marie-Claire and Tan, Weizhen and Gribouval, Olivier and Boyer, Olivia and Revy, Patrick and Jobst-Schwan, Tilman and Schmidt, Johanna Magdalena and Lawson, Jennifer A. and Schanze, Denny and Ashraf, Shazia and Ullmann, Jeremy F. P. and Hoogstraten, Charlotte A. and Boddaert, Nathalie and Collinet, Bruno and Martin, Gaelle and Liger, Dominique and Lovric, Svjetlana and Furlano, Monica and Guerrera, I. Chiara and Sanchez-Ferras, Oraly and Hu, Jennifer F. and Boschat, Anne-Claire and Sanquer, Sylvia and Menten, Bjorn and Vergult, Sarah and De Rocker, Nina and Airik, Merlin and Hermle, Tobias and Shril, Shirlee and Widmeier, Eugen and Gee, Heon Yung and Choi, Won-Il and Sadowski, Carolin E. and Pabst, Werner L. and Warejko, Jillian K. and Daga, Ankana and Basta, Tamara and Matejas, Verena and Scharmann, Karin and Kienast, Sandra D. and Behnam, Babak and Beeson, Brendan and Begtrup, Amber and Bruce, Malcolm and Ch'Ng, Gaik-Siew and Lin, Shuan-Pei and Chang, Jui-Hsing and Chen, Chao-Huei and Cho, Megan T. and Gaffney, Patrick M. and Gipson, Patrick E. and Hsu, Chyong-Hsin and Kari, Jameela A. and Ke, Yu-Yuan and Kiraly-Borri, Cathy and Lai, Wai-Ming and Lemyre, Emmanuelle and Littlejohn, Rebecca Okashah and Masri, Amira and Moghtaderi, Mastaneh and Nakamura, Kazuyuki and Ozaltin, Fatih and Praet, Marleen and Prasad, Chitra and Prytula, Agnieszka and Roeder, Elizabeth R. and Rump, Patrick and Schnur, Rhonda E. and Shiihara, Takashi and Sinha, Manish D. and Soliman, Neveen A. and Soulami, Kenza and Sweetser, David A. and Tsai, Wen-Hui and Tsai, Jeng-Daw and Topaloglu, Rezan and Vester, Udo and Viskochil, David H. and Vatanavicharn, Nithiwat and Waxler, Jessica L. and Wierenga, Klaas J. and Wolf, Matthias T. F. and Wong, Sik-Nin and Leidel, Sebastian A. and Truglio, Gessica and Dedon, Peter C. and Poduri, Annapurna and Mane, Shrikant and Lifton, Richard P. and Bouchard, Maxime and Kannu, Peter and Chitayat, David and Magen, Daniella and Callewaert, Bert and Van Tilbeurgh, Herman and Zenker, Martin and Antignac, Corinne and Hildebrandt, Friedhelm},
doi = {10.1038/ng.3933},
faupublication = {yes},
journal = {Nature Genetics},
note = {Created from Fastlane, Scopus look-up},
pages = {1529-1538},
peerreviewed = {Yes},
title = {{Mutations} in {KEOPS}-complex genes cause nephritic syndrome with primary microcephaly},
volume = {49},
year = {2017}
}
@article{faucris.109929424,
abstract = {The risk of epilepsy among individuals with intellectual disability (ID) is approximately ten times that of the general population. From a cohort of >5,000 families affected by neurodevelopmental disorders, we identified six consanguineous families harboring homozygous inactivating variants in MBOAT7, encoding lysophosphatidylinositol acyltransferase (LPIAT1). Subjects presented with ID frequently accompanied by epilepsy and autistic features. LPIAT1 is a membrane-bound phospholipid-remodeling enzyme that transfers arachidonic acid (AA) to lysophosphatidylinositol to produce AA-containing phosphatidylinositol. This study suggests a role for AA-containing phosphatidylinositols in the development of ID accompanied by epilepsy and autistic features.},
author = {Johansen, Anide and Rosti, Rasim O. and Musaev, Damir and Sticca, Evan and Harripaul, Ricardo and Zaki, Maha and Caglayan, Ahmet Okay and Azam, Matloob and Sultan, Tipu and Froukh, Tawfiq and Reis, André and Popp, Bernt and Ahmed, Iltaf and John, Peter and Ayub, Muhammad and Ben-Omran, Tawfeg and Vincent, John B. and Gleeson, Joseph G. and Abou Jamra, Rami},
doi = {10.1016/j.ajhg.2016.07.019},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9331},
pages = {912-916},
peerreviewed = {Yes},
title = {{Mutations} in {MBOAT7}, {Encoding} {Lysophosphatidylinositol} {Acyltransferase} {I}, {Lead} to {Intellectual} {Disability} {Accompanied} by {Epilepsy} and {Autistic} {Features}},
volume = {99},
year = {2016}
}
@article{faucris.218982067,
abstract = {PIK3C2A is a class II member of the phosphoinositide 3-kinase (PI3K) family that catalyzes the phosphorylation of phosphatidylinositol (PI) into PI(3)P and the phosphorylation of PI(4)P into PI(3,4)P2. At the cellular level, PIK3C2A is critical for the formation of cilia and for receptor mediated endocytosis, among other biological functions. We identified homozygous loss-of-function mutations in PIK3C2A in children from three independent consanguineous families with short stature, coarse facial features, cataracts with secondary glaucoma, multiple skeletal abnormalities, neurological manifestations, among other findings. Cellular studies of patient-derived fibroblasts found that they lacked PIK3C2A protein, had impaired cilia formation and function, and demonstrated reduced proliferative capacity. Collectively, the genetic and molecular data implicate mutations in PIK3C2A in a new Mendelian disorder of PI metabolism, thereby shedding light on the critical role of a class II PI3K in growth, vision, skeletal formation and neurological development. In particular, the considerable phenotypic overlap, yet distinct features, between this syndrome and Lowe's syndrome, which is caused by mutations in the PI-5-phosphatase OCRL, highlight the key role of PI metabolizing enzymes in specific developmental processes and demonstrate the unique non-redundant functions of each enzyme. This discovery expands what is known about disorders of PI metabolism and helps unravel the role of PIK3C2A and class II PI3Ks in health and disease.},
author = {Tiosano, Dov and Baris, Hagit N. and Chen, Anlu and Hitzert, Marrit M. and Schüler, Markus and Gulluni, Federico and Wiesener, Antje and Bergua, Antonio and Mory, Adi and Copeland, Brett and Gleeson, Joseph G. and Rump, Patrick and Van Meer, Hester and Sival, Deborah A. and Haucke, Volker and Kriwinsky, Josh and Knaup, Karl and Reis, André and Hauer, Nadine and Hirsch, Emilio and Roepman, Ronald and Pfundt, Rolph and Thiel, Christian and Wiesener, Michael S. and Aslanyan, Mariam G. and Buchner, David A.},
doi = {10.1371/journal.pgen.1008088},
faupublication = {yes},
journal = {PLoS Genetics},
note = {CRIS-Team Scopus Importer:2019-05-28},
pages = {e1008088-},
peerreviewed = {Yes},
title = {{Mutations} in {PIK3C2A} cause syndromic short stature, skeletal abnormalities, and cataracts associated with ciliary dysfunction},
volume = {15},
year = {2019}
}
@article{faucris.203416624,
abstract = {Variants affecting the function of different subunits of the BAF chromatin-remodelling complex lead to various neurodevelopmental syndromes, including Coffin-Siris syndrome. Furthermore, variants in proteins containing PHD fingers, motifs recognizing specific histone tail modifications, have been associated with several neurological and developmental-delay disorders. Here, we report eight heterozygous de novo variants (one frameshift, two splice site, and five missense) in the gene encoding the BAF complex subunit double plant homeodomain finger 2 (DPF2). Affected individuals share common clinical features described in individuals with Coffin-Siris syndrome, including coarse facial features, global developmental delay, intellectual disability, speech impairment, and hypoplasia of fingernails and toenails. All variants occur within the highly conserved PHD1 and PHD2 motifs. Moreover, missense variants are situated close to zinc binding sites and are predicted to disrupt these sites. Pull-down assays of recombinant proteins and histone peptides revealed that a subset of the identified missense variants abolish or impaire DPF2 binding to unmodified and modified H3 histone tails. These results suggest an impairment of PHD finger structural integrity and cohesion and most likely an aberrant recognition of histone modifications. Furthermore, the overexpression of these variants in HEK293 and COS7 cell lines was associated with the formation of nuclear aggregates and the recruitment of both wild-type DPF2 and BRG1 to these aggregates. Expression analysis of truncating variants found in the affected individuals indicated that the aberrant transcripts escape nonsense-mediated decay. Altogether, we provide compelling evidence that de novo variants in DPF2 cause Coffin-Siris syndrome and propose a dominant-negative mechanism of pathogenicity.},
author = {Vasileiou, Georgia and Vergarajauregui, Silvia and Endele, Sabine and Popp, Bernt and Büttner, Christian and Ekici, Arif Bülent and Gerard, Marion and Bramswig, Nuria C. and Albrecht, Beate and Clayton-Smith, Jill and Morton, Jenny and Tomkins, Susan and Low, Karen and Weber, Astrid and Wenzel, Maren and Altmueller, Janine and Li, Yun and Wollnik, Bernd and Hoganson, George and Plona, Maria-Renee and Cho, Megan T. and Thiel, Christian and Luedecke, Hermann-Josef and Strom, Tim M. and Calpena, Eduardo and Wilkie, Andrew O. M. and Wieczorek, Dagmar and Engel, Felix and Reis, André},
doi = {10.1016/j.ajhg.2018.01.014},
faupublication = {yes},
journal = {American Journal of Human Genetics},
pages = {468-479},
peerreviewed = {Yes},
title = {{Mutations} in the {BAF}-{Complex} {Subunit} {DPF2} {Are} {Associated} with {Coffin}-{Siris} {Syndrome}},
volume = {102},
year = {2018}
}
@inproceedings{faucris.228303270,
address = {LONDON},
author = {Vasileiou, G. and Vergarajauregui, S. and Endele, Sabine and Popp, Bernt and Büttner, Christian and Ekici, Arif Bülent and Gerard, M. and Bramswig, N. C. and Albrecht, B. and Clayton-Smith, J. and Morton, J. and Tomkins, S. and Low, K. and Weber, A. and Wenzel, M. and Altmueller, J. and Li, Y. and Wollnik, B. and Hoganson, G. and Plona, M. and Cho, M. T. and Thiel, Christian and Luedecke, H. and Strom, T. M. and Calpena, E. and Wilkie, A. O. M. and Wieczorek, D. and Engel, Felix and Wiesmann da Silva Reis, André},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2018-06-16/2018-06-19},
doi = {10.1016/j.ajhg.2018.01.014},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {805-806},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{Mutations} in the {BAF}-complex subunit {DPF2} are associated with {Coffin}-{Siris} syndrome},
venue = {Milan, ITALY},
year = {2019}
}
@article{faucris.108928204,
abstract = {Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.},
author = {Meyer, Esther and Carss, Keren J. and Rankin, Julia and Nichols, John M. E. and Grozeva, Detelina and Joseph, Agnel P. and Mencacci, Niccolo E. and Papandreou, Apostolos and Ng, Joanne and Barra, Serena and Ngoh, Adeline and Ben-Pazi, Hilla and Willemsen, Michel A. and Arkadir, David and Barnicoat, Angela and Bergman, Hagai and Bhate, Sanjay and Boys, Amber and Darin, Niklas and Foulds, Nicola and Gutowski, Nicholas and Hills, Alison and Houlden, Henry and Hurst, Jane A. and Israe, Zvi and Kaminska, Margaret and Limousin, Patricia and Lumsden, Daniel and Mckee, Shane and Misra, Shibalik and Mohammed, Shekeeb S. and Nakou, Vasiliki and Nicolai, Joost and Nilsson, Magnus and Pall, Hardev and Peall, Kathryn J. and Peters, Gregory B. and Prabhakar, Prab and Reuter, Miriam and Rump, Patrick and Sege, Reeval and Sinnema, Margje and Smith, Martin and Turnpenny, Peter and White, Susan M. and Wieczorek, Dagmar and Wiethoff, Sarah and Wilson, Brian T. and Winter, Gidon and Wragg, Christopher and Pope, Simon and Heales, Simon J. H. and Morrogh, Deborah and Pittman, Alan and Carr, Lucinda J. and Perez-Duenas, Belen and Lin, Jean-Pierre and Reis, André and Gahl, William A. and Toro, Camilo and Bhatia, Kailash P. and Wood, Nicholas W. and Kamsteeg, Erik-Jan and Chong, Wui K. and Gissen, Paul and Topf, Maya and Dale, Russell C. and Chubby, Jonathan R. and Raymond, F. Lucy and Kurian, Manju A.},
doi = {10.1038/ng.3740},
faupublication = {yes},
journal = {Nature Genetics},
note = {EVALuna2:9343},
peerreviewed = {Yes},
title = {{Mutations} in the histone methyltransferase gene {KMT2B} cause complex early-onset dystonia},
year = {2016}
}
@article{faucris.242697225,
abstract = {Mycobacteria survive in macrophages despite triggering pattern recognition receptors and T cell-derived IFN-γ production. Mycobacterial cord factor trehalose-6,6-dimycolate (TDM) binds the C-type lectin receptor MINCLE and induces inflammatory gene expression. However, the impact of TDM on IFN-γ-induced macrophage activation is not known. In this study, we have investigated the cross-regulation of the mouse macrophage transcriptome by IFN-γ and by TDM or its synthetic analogue trehalose-6,6-dibehenate (TDB). As expected, IFN-γ induced genes involved in Ag presentation and antimicrobial defense. Transcriptional programs induced by TDM and TDB were highly similar but clearly distinct from the response to IFN-γ. The glycolipids enhanced expression of a subset of IFN-γ-induced genes associated with inflammation. In contrast, TDM/TDB exerted delayed inhibition of IFN-γ-induced genes, including pattern recognition receptors, MHC class II genes, and IFN-γ-induced GTPases, with antimicrobial function. TDM downregulated MHC class II cell surface expression and impaired T cell activation by peptide-pulsed macrophages. Inhibition of the IFN-γ-induced GTPase GBP1 occurred at the level of transcription by a partially MINCLE-dependent mechanism that may target IRF1 activity. Although activation of STAT1 was unaltered, deletion of Socs1 relieved inhibition of GBP1 expression by TDM. Nonnuclear Socs1 was sufficient for inhibition, suggesting a noncanonical, cytoplasmic mechanism. Taken together, unbiased analysis of transcriptional reprogramming revealed a significant degree of negative regulation of IFN-γ-induced Ag presentation and antimicrobial gene expression by the mycobacterial cord factor that may contribute to mycobacterial persistence.},
author = {Huber, Alexandra and Killy, Barbara and Grummel, Nadine and Bodendorfer, Barbara and Paul, Sushmita and Wiesmann, Veit and Naschberger, Elisabeth and Zimmer, Jana and Wirtz, Stefan and Schleicher, Ulrike and Vera, Julio and Ekici, Arif Bülent and Dalpke, Alexander and Lang, Roland},
doi = {10.4049/jimmunol.2000337},
faupublication = {yes},
journal = {Journal of Immunology},
note = {CRIS-Team Scopus Importer:2020-09-18},
pages = {1580-1592},
peerreviewed = {Yes},
title = {{Mycobacterial} {Cord} {Factor} {Reprograms} the {Macrophage} {Response} to {IFN}-γ towards {Enhanced} {Inflammation} yet {Impaired} {Antigen} {Presentation} and {Expression} of {GBP1}},
volume = {205},
year = {2020}
}
@article{faucris.242393292,
abstract = {Generalized pustular psoriasis (GPP) is a severe multi-systemic inflammatory disease characterized by neutrophilic pustulosis and triggered by pro-inflammatory IL-36 cytokines in skin. While 19%–41% of affected individuals harbor bi-allelic mutations in IL36RN, the genetic cause is not known in most cases. To identify and characterize new pathways involved in the pathogenesis of GPP, we performed whole-exome sequencing in 31 individuals with GPP and demonstrated effects of mutations in MPO encoding the neutrophilic enzyme myeloperoxidase (MPO). We discovered eight MPO mutations resulting in MPO -deficiency in neutrophils and monocytes. MPO mutations, primarily those resulting in complete MPO deficiency, cumulatively associated with GPP (p = 1.85E−08; OR = 6.47). The number of mutant MPO alleles significantly differed between 82 affected individuals and >4,900 control subjects (p = 1.04E−09); this effect was stronger when including IL36RN mutations (1.48E−13) and correlated with a younger age of onset (p = 0.0018). The activity of four proteases, previously implicated as activating enzymes of IL-36 precursors, correlated with MPO deficiency. Phorbol-myristate-acetate-induced formation of neutrophil extracellular traps (NETs) was reduced in affected cells (p = 0.015), and phagocytosis assays in MPO-deficient mice and human cells revealed altered neutrophil function and impaired clearance of neutrophils by monocytes (efferocytosis) allowing prolonged neutrophil persistence in inflammatory skin. MPO mutations contribute significantly to GPP's pathogenesis. We implicate MPO as an inflammatory modulator in humans that regulates protease activity and NET formation and modifies efferocytosis. Our findings indicate possible implications for the application of MPO inhibitors in cardiovascular diseases. MPO and affected pathways represent attractive targets for inducing resolution of inflammation in neutrophil-mediated skin diseases.},
author = {Haskamp, Stefan and Bruns, Heiko and Hahn, Madelaine and Hoffmann, Markus and Gregor, Anne and Löhr, Sabine and Hahn, Jonas and Ringer, Mark and Flamann, Cindy and Frey, Benjamin and Lesner, Adam and Thiel, Christian and Ekici, Arif Bülent and von Hörsten, Stephan and Aßmann, Gunter and Riepe, Claudia and Euler, Maximilien and Schäkel, Knut and Philipp, Sandra and Prinz, Jörg C. and Mößner, Rotraut and Kersting, Florina and Sticherling, Michael and Sefiani, Abdelaziz and Lyahyai, Jaber and Sondermann, Wiebke and Oji, Vinzenz and Schulz, Peter and Wilsmann-Theis, Dagmar and Sticht, Heinrich and Schett, Georg and Reis, André and Uebe, Steffen and Frey, Silke and Hüffmeier, Ulrike and Schauer, Christine},
doi = {10.1016/j.ajhg.2020.07.001},
faupublication = {yes},
journal = {American Journal of Human Genetics},
keywords = {ACH; acrodermatitis continua suppurativa Hallopeau; activation of IL-36 precursors; acute generalized 4 exanthematous pustulosis; AGEP; efferocytosis; generalized pustular psoriasis; GPP; impaired NETosis; MPO deficiency; myeloperoxidase; oligogenic inheritance},
note = {CRIS-Team Scopus Importer:2020-09-11},
pages = {527-538},
peerreviewed = {Yes},
title = {{Myeloperoxidase} {Modulates} {Inflammation} in {Generalized} {Pustular} {Psoriasis} and {Additional} {Rare} {Pustular} {Skin} {Diseases}},
volume = {107},
year = {2020}
}
@article{faucris.309907021,
author = {Unterweger, Harald and Janko, Christina and Civelek, Mehtap and Cicha, Iwona and Spielvogel, Helmut and Tietze, Rainer and Friedrich, Bernhard and Alexiou, Christoph},
doi = {10.2217/nnm-2023-0109},
faupublication = {yes},
journal = {Nanomedicine},
keywords = {age-related macular degeneration; diabetic retinopathy; eye infections; glaucoma; keratitis; nanoparticles},
note = {CRIS-Team Scopus Importer:2023-09-01},
pages = {783-788},
peerreviewed = {Yes},
title = {{Nanomaterial}-based ophthalmic therapies},
volume = {18},
year = {2023}
}
@article{faucris.208513166,
abstract = {Genetic integrity of induced pluripotent stem cells (iPSCs) is essential for their validity as disease models and for potential therapeutic use. We describe the comprehensive analysis in the ForIPS consortium: an iPSC collection from donors with neurological diseases and healthy controls. Characterization included pluripotency confirmation, fingerprinting, conventional and molecular karyotyping in all lines. In the majority, somatic copy number variants (CNVs) were identified. A subset with available matched donor DNA was selected for comparative exome sequencing. We identified single nucleotide variants (SNVs) at different allelic frequencies in each clone with high variability in mutational load. Low frequencies of variants in parental fibroblasts highlight the importance of germline samples. Somatic variant number was independent from reprogramming, cell type and passage. Comparison with disease genes and prediction scores suggest biological relevance for some variants. We show that high-throughput sequencing has value beyond SNV detection and the requirement to individually evaluate each clone.},
author = {Popp, Bernt and Krumbiegel, Mandy and Grosch, Janina and Sommer, Annika and Uebe, Steffen and Kohl, Zacharias and Ploetz, Sonja and Farrell, Michaela and Trautmann, Udo and Kraus, Cornelia and Ekici, Arif Bülent and Asadollahi, Reza and Regensburger, Martin and Guenther, Katharina and Rauch, Anita and Edenhofer, Frank and Winkler, Jürgen and Winner, Beate and Reis, André},
doi = {10.1038/s41598-018-35506-0},
faupublication = {yes},
journal = {Scientific Reports},
note = {EVALuna2:34839},
peerreviewed = {Yes},
title = {{Need} for high-resolution {Genetic} {Analysis} in {iPSC}: {Results} and {Lessons} from the {ForIPS} {Consortium}},
volume = {8},
year = {2018}
}
@article{faucris.267246605,
abstract = {Preterm neonates are at a high risk for nephron loss under adverse clinical conditions. Renal damage potentially collides with postnatal nephrogenesis. Recent animal studies suggest that nephron loss within this vulnerable phase leads to renal damage later in life. Nephrogenic pathways are commonly reactivated after kidney injury supporting renal regeneration. We hypothesized that nephron loss during nephrogenesis affects renal development, which, in turn, impairs tissue repair after secondary injury. Neonates prior to 36 wk of gestation show an active nephrogenesis. In rats, nephrogenesis is ongoing until day 10 after birth. Mimicking the situation of severe nephron loss during nephrogenesis, male pups were uninephrectomized at day 1 of life (UNXd1). A second group of males was uninephrectomized at postnatal day 14 (UNXd14), after terminated nephrogenesis. Agematched controls were sham operated. Three days after uninephrectomy transcriptional changes in the right kidney were analyzed by RNA-sequencing, followed by functional pathway analysis. In UNXd1, 1,182 genes were differentially regulated, but only 143 genes showed a regulation both in UNXd1 and UNXd14. The functional groups “renal development” and “kidney injury” were among the most differentially regulated groups and revealed distinctive alterations. Reduced expression of candidate genes concerning renal development (Bmp7, Gdnf, Pdgf-B, Wt1) and injury (nephrin, podocin, Tgf-b 1) were detected. The downregulation of Bmp7 and Gdnf persisted until day 28. In UNXd14, Six2 was upregulated and Pax2 was downregulated. We conclude that nephron loss during nephrogenesis affects renal development and induces a specific regulation of genes that might hinder tissue repair after secondary kidney injury.},
author = {Raming, Roman and Cordasic, Nada and Kirchner, Philipp and Ekici, Arif Bülent and Fahlbusch, Fabian and Wölfle, Joachim and Hilgers, Karl Friedrich and Hartner, Andrea and Menendez-Castro, Carlos},
doi = {10.1152/physiolgenomics.00059.2021},
faupublication = {yes},
journal = {Physiological Genomics},
keywords = {Neonatal nephron loss; Neonatal uninephrectomy; Nephrogenesis; Renal regeneration; RNA-sequencing},
note = {CRIS-Team Scopus Importer:2021-12-17},
pages = {509-517},
peerreviewed = {Yes},
title = {{Neonatal} nephron loss during active nephrogenesis results in altered expression of renal developmental genes and markers of kidney injury},
volume = {53},
year = {2021}
}
@article{faucris.292852658,
abstract = {Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11.\nPathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking.\nIn order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI.\nCompared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients.\nCONCLUSIONS\nBACKGROUND\nMETHODS\nRESULTS},
author = {Winner, Beate and Marterstock, Dominique and Kopp, Christoph and Dörfler, Arnd and Regensburger, Martin and Krumm, Laura and Schmidt, Manuel and Schmid, Andreas and Spatz, Imke and Marterstock, Dominique and Kopp, Christoph and Kohl, Zacharias and Dörfler, Arnd},
doi = {10.3390/nu14224803},
faupublication = {yes},
journal = {Nutrients},
keywords = {SPG11; adipokines; bioimpedance spectroscopy; hypothalamus; leptin; obesity},
peerreviewed = {Yes},
title = {{Neurometabolic} {Dysfunction} in {SPG11} {Hereditary} {Spastic} {Paraplegia}.},
volume = {14},
year = {2022}
}
@article{faucris.245148422,
abstract = {Purpose: A few de novo missense variants in the cytoplasmic FMRP-interacting protein 2 (CYFIP2) gene have recently been described as a novel cause of severe intellectual disability, seizures, and hypotonia in 18 individuals, with p.Arg87 substitutions in the majority. Methods: We assembled data from 19 newly identified and all 18 previously published individuals with CYFIP2 variants. By structural modeling and investigation of WAVE-regulatory complex (WRC)-mediated actin polymerization in six patient fibroblast lines we assessed the impact of CYFIP2 variants on the WRC. Results: Sixteen of 19 individuals harbor two previously described and 11 novel (likely) disease-associated missense variants. We report p.Asp724 as second mutational hotspot (4/19 cases). Genotype–phenotype correlation confirms a consistently severe phenotype in p.Arg87 patients but a more variable phenotype in p.Asp724 and other substitutions. Three individuals with milder phenotypes carry putative loss-of-function variants, which remain of unclear pathogenicity. Structural modeling predicted missense variants to disturb interactions within the WRC or impair CYFIP2 stability. Consistent with its role in WRC-mediated actin polymerization we substantiate aberrant regulation of the actin cytoskeleton in patient fibroblasts. Conclusion: Our study expands the clinical and molecular spectrum of CYFIP2-related neurodevelopmental disorder and provides evidence for aberrant WRC-mediated actin dynamics as contributing cellular pathomechanism.},
author = {Begemann, Anaïs and Sticht, Heinrich and Begtrup, Amber and Vitobello, Antonio and Faivre, Laurence and Banka, Siddharth and Alhaddad, Bader and Asadollahi, Reza and Becker, Jessica and Bierhals, Tatjana and Brown, Kathleen E. and Bruel, Ange Line and Brunet, Theresa and Carneiro, Maryline and Cremer, Kirsten and Day, Robert and Denommé-Pichon, Anne Sophie and Dyment, Dave A. and Engels, Hartmut and Fisher, Rachel and Goh, Elaine S. and Hajianpour, M. J. and Haertel, Lucia Ribeiro Machado and Hauer, Nadine and Hempel, Maja and Herget, Theresia and Johannsen, Jessika and Kraus, Cornelia and Le Guyader, Gwenaël and Lesca, Gaetan and Mau-Them, Frédéric Tran and McDermott, John Henry and McWalter, Kirsty and Meyer, Pierre and Õunap, Katrin and Popp, Bernt and Reimand, Tiia and Riedhammer, Korbinian M. and Russo, Martina and Sadleir, Lynette G. and Saenz, Margarita and Schiff, Manuel and Schuler, Elisabeth and Syrbe, Steffen and Van der Ven, Amelie Theresa and Verloes, Alain and Willems, Marjolaine and Zweier, Christiane and Steindl, Katharina and Zweier, Markus and Rauch, Anita},
doi = {10.1038/s41436-020-01011-x},
faupublication = {yes},
journal = {Genetics in Medicine},
keywords = {CYFIP2; epilepsy; intellectual disability; WASF; WAVE-regulatory complex (WRC)},
note = {CRIS-Team Scopus Importer:2020-11-13},
peerreviewed = {Yes},
title = {{New} insights into the clinical and molecular spectrum of the novel {CYFIP2}-related neurodevelopmental disorder and impairment of the {WRC}-mediated actin dynamics},
year = {2020}
}
@article{faucris.106328244,
abstract = {Background Ophthalmology, principally, is a very successful subdiscipline in medicine. Nonetheless, there are still unmet medical needs which necessitate translational research. Methods The funding instrument of a Research Unit (RU) of the German Research Foundation (DFG) is presented as exemplified by the RU 2240 at the Department of Ophthalmology at the University of Cologne. Results The Research Unit integrates different research groups working on pathologic ocular inflammation, macrophages/microglia and (lymph)angiogenesis to collaborate in a synergistic way. Rotation positions allow young clinicians to rotate into research labs for a defined period of time. A Research Unit is also a powerful strategic tool to strengthen clinical and experimental ophthalmology at individual medical faculties. Conclusions The funding instrument of a Research Unit is highly suitable for fostering translational research in a medical subdiscipline such as ophthalmology, supporting the next generation of (clinician) scientists in ophthalmology and finding new cures for our patients.},
author = {Cursiefen, Claus and Bock, Felix and Clahsen, Thomas and Regenfuss, Birgit and Reis, André and Steven, Philipp and Heindl, Ludwig M. and Bosch, Jacobus J. and Hos, Deniz and Eming, Sabine and Grajewski, Rafael and Heiligenhaus, Arnd and Fauser, Sascha and Austin, Jennifer and Langmann, Thomas},
doi = {10.1055/s-0043-108247},
faupublication = {yes},
journal = {Klinische Monatsblätter für Augenheilkunde},
note = {EVALuna2:9372},
pages = {679-685},
peerreviewed = {Yes},
title = {{New} {Therapeutic} {Approaches} in {Inflammatory} {Diseases} of the {Eye} - {Targeting} {Lymphangiogenesis} and {Cellular} {Immunity}: {Research} {Unit} {FOR} 2240 {Presents} {Itself}},
volume = {234},
year = {2017}
}
@article{faucris.314059387,
abstract = {Background and Aims: Inflammatory bowel diseases (IBD) are characterized by mucosal inflammation and sequential fibrosis formation, but the exact role of the hyperactive NLRP3 inflammasome in these processes is unclear. Thus, we studied the expression and function of the NLRP3 inflammasome in the context of inflammation and fibrosis in IBD. Methods: We analysed intestinal NLRP3 expression in mucosal immune cells and fibroblasts from IBD patients and NLRP3-associated gene expression via single-cell RNA sequencing and microarray analyses. Furthermore, cytokine secretion of NLRP3 inhibitor treated blood and mucosal cells, as well as proliferation, collagen production, and cell death of NLRP3 inhibitor treated intestinal fibroblasts from IBD patients were studied. Results: We found increased NLRP3 expression in the inflamed mucosa of IBD patients and NLRP3 inhibition led to reduced IL-1β and IL-18 production in blood cells and diminished the bioactive form of mucosal IL-1β. Single cell analysis identified overlapping expression patterns of NLRP3 and IL-1β in classically activated intestinal macrophages and we also detected NLRP3 expression in CD163+ macrophages. In addition, NLRP3 expression was also found in intestinal fibroblasts from IBD patients. Inhibition of NLRP3 led to reduced proliferation of intestinal fibroblasts, which was associated with a marked decrease in production of collagen type I and type VI in IBD patients. Moreover, NLRP3 inhibition in intestinal fibroblasts induced autophagy, a cellular process involved in collagen degradation. Conclusions: In the presented study, we demonstrate that inhibiting NLRP3 might pave the way for novel therapeutic approaches in IBD, especially to prevent the severe complication of intestinal fibrosis formation.},
author = {Weber, Simone and Sitte, Selina and Vögele, Anna-Lena and Sologub, Ludmilla and Wilfer, Angelika and Rath, Timo and Nägel, Andreas and Zundler, Sebastian and Franchi, Luigi and Opipari, Anthony W. and Sonnewald, Sophia and Reid, Stephen and Hartmann, Arndt and Eichhorn, Philip and Handtrack, Claudia and Weber, Klaus and Grützmann, Robert and Neufert, Clemens and Schellerer, Vera and Naschberger, Elisabeth and Ekici, Arif Bülent and Büttner, Christian and Neurath, Markus and Atreya, Raja},
doi = {10.1093/ecco-jcc/jjad164},
faupublication = {yes},
journal = {Journal of Crohns & Colitis},
keywords = {fibroblasts; fibrosis; IL-18; IL-1β; Inflammatory bowel diseases; mucosal immune system; NLRP3 inflammasome; small molecule inhibitor},
note = {CRIS-Team Scopus Importer:2023-11-17},
peerreviewed = {Yes},
title = {{NLRP3} {Inhibition} {Leads} to {Impaired} {Mucosal} {Fibroblast} {Function} in {Patients} with {Inflammatory} {Bowel} {Diseases}},
year = {2023}
}
@article{faucris.120808424,
author = {Pasutto, Francesca and Flinter, Frances and Rauch, Anita and Reis, André},
doi = {10.1002/ajmg.a.38529},
faupublication = {yes},
journal = {American Journal of Medical Genetics Part A},
note = {EVALuna2:9392},
peerreviewed = {Yes},
title = {{Novel} {STRA6} null mutations in the original family described with {Matthew}-{Wood} syndrome},
year = {2017}
}
@article{faucris.208512795,
abstract = {BACKGROUND: Low vision in children can be accompanied by pallor of the optic disc with little or no characteristic morphologic changes of the retina. A variety of diseases can be the underlying cause, including hereditary optic atrophy, Leber's congenital amaurosis (LCA), achromatopsia, and calcium channel, voltage-dependent, L-type, alpha-1F subunit gene (CACNA1F)-associated retinopathy (most widely known as incomplete congenital stationary night blindness: iCSNB). Differentiation at early age is desirable due to large differences in prognosis, but may be difficult because phenotypes overlap and electrophysiological testing is challenging in young patients. We present the case of a 6-year-old boy with unexplained low vision and pallor of the optic disc who originally had been diagnosed with hereditary optic atrophy in the absence of recordable full-field electroretinography (ERG) due to poor patient cooperation.
MATERIALS AND METHODS: Standard Sanger sequencing excluded mutations in the OPA1 gene (autosomal-dominant optic atrophy). To identify the underlying genetic cause, whole-exome sequencing was performed on patient's DNA. Recording of the full-field ERG was successfully performed 6 months later.
RESULTS: We identified a novel truncating mutation in CACNA1F gene (NM{\_}001256789: c.3895C > T in exon 33) which led to the correct diagnosis of CACNA1F-associated retinopathy in the young boy. ERG recordings showed a negative scotopic mixed response with preserved oscillatory potentials and a flicker ERG with reduced amplitude and biphasic waveform, compatible with a CACNA1F-asssociated phenotype.
CONCLUSIONS: We show that genetic testing may help to differentiate between optic atrophy, LCA, and CACNA1F-associated retinopathy at a much earlier age, in absence of electrophysiological examination and by widely overlapping phenotypes.},
author = {Pasutto, Francesca and Ekici, Arif Bülent and Reis, André and Kremers, Jan and Huchzermeyer, Cord},
doi = {10.1080/13816810.2018.1520263},
faupublication = {yes},
journal = {Ophthalmic Genetics},
note = {EVALuna2:34838},
pages = {1-8},
peerreviewed = {Yes},
title = {{Novel} truncating mutation in {CACNA1F} in a young male patient diagnosed with optic atrophy},
year = {2018}
}
@article{faucris.124008544,
abstract = {Many eukaryotic cell-surface proteins are anchored to the membrane via glycosylphosphatidylinositol (GPI). There are at least 26 genes involved in biosynthesis and remodeling of GPI anchors. Hypomorphic coding mutations in seven of these genes have been reported to cause decreased expression of GPI anchored proteins (GPI-APs) on the cell surface and to cause autosomal-recessive forms of intellectual disability (ARID). We performed homozygosity mapping and exome sequencing in a family with encephalopathy and non-specific ARID and identified a homozygous 3 bp deletion (p.Leu197del) in the GPI remodeling gene PGAP1. PGAP1 was not described in association with a human phenotype before. PGAP1 is a deacylase that removes an acyl-chain from the inositol of GPI anchors in the endoplasmic reticulum immediately after attachment of GPI to proteins. In silico prediction and molecular modeling strongly suggested a pathogenic effect of the identified deletion. The expression levels of GPI-APs on B lymphoblastoid cells derived from an affected person were normal. However, when those cells were incubated with phosphatidylinositol-specific phospholipase C (PI-PLC), GPI-APs were cleaved and released from B lymphoblastoid cells from healthy individuals whereas GPI-APs on the cells from the affected person were totally resistant. Transfection with wild type PGAP1 cDNA restored the PI-PLC sensitivity. These results indicate that GPI-APs were expressed with abnormal GPI structure due to a null mutation in the remodeling gene PGAP1. Our results add PGAP1 to the growing list of GPI abnormalities and indicate that not only the cell surface expression levels of GPI-APs but also the fine structure of GPI-anchors is important for the normal neurological development.},
author = {Murakami, Yoshiko and Tawamie, Hasan and Maeda, Yusuke and Büttner, Christian and Buchert, Rebecca and Radwan, Farah and Schaffer, Susann and Sticht, Heinrich and Aigner, Michael and Reis, André and Kinoshita, Taroh and Abou Jamra, Rami},
doi = {10.1371/journal.pgen.1004320},
faupublication = {yes},
journal = {PLoS Genetics},
note = {EVALuna2:9210},
pages = {e1004320},
peerreviewed = {Yes},
title = {{Null} mutation in {PGAP1} impairing {Gpi}-anchor maturation in patients with intellectual disability and encephalopathy},
volume = {10},
year = {2014}
}
@article{faucris.261566523,
abstract = {Recently, oligodendrocytes (Ol) have been attributed potential immunomodulatory effects. Yet, the exact mode of interaction with pathogenic CNS infiltrating lymphocytes remains unclear. Here, we attempt to dissect mechanisms of Ol modulation during neuroinflammation and characterize the interaction of Ol with pathogenic T cells. RNA expression analysis revealed an upregulation of immune-modulatory genes and adhesion molecules (AMs), ICAM-1 and VCAM-1, in Ol when isolated from mice undergoing experimental autoimmune encephalomyelitis (EAE). To explore whether AMs are involved in the interaction of Ol with infiltrating T cells, we performed co-culture studies on mature Ol and Th1 cells. Live cell imaging analysis showed direct interaction between both cell types. Eighty percentage of Th1 cells created contacts with Ol that lasted longer than 15 min, which may be regarded as physiologically relevant. Exposure of Ol to Th1 cells or their supernatant resulted in a significant extension of Ol processes, and upregulation of AMs as well as other immunomodulatory genes. Our observations indicate that blocking of oligodendroglial ICAM-1 can reduce the number of Th1 cells initially contacting the Ol. These results suggest that AMs may play a role in the interaction between Ol and Th1 cells. We identified Ol interacting with CD4+ cells in vivo in spinal cord tissue of EAE diseased mice indicating that our in vitro findings are of interest to further scientific research in this field. Further characterization and understanding of Ol interaction with infiltrating cells may lead to new therapeutic strategies enhancing Ol protection and remyelination potential. Oligodendrocytes regulate immune modulatory genes and adhesion molecules during autoimmune neuroinflammation Oligodendrocytes interact with Th1 cells in vitro in a physiologically relevant manner Adhesion molecules may be involved in Ol-Th1 cell interaction.},
author = {Alvarado, M. N. Gonzalez and Aprato, J. and Baumeister, M. and Ekici, Arif Bülent and Kirchner, P. and Hoffmann, Alana and Winkler, Jürgen and Wegner, M. and Haase, S. and Linker, R.},
doi = {10.1002/glia.24120},
faupublication = {yes},
journal = {Glia},
keywords = {adhesion molecules; autoimmune neuroinflammation; EAE; oligodendrocytes; Th1 cells},
note = {CRIS-Team WoS Importer:2021-07-16},
pages = {E445-E446},
peerreviewed = {unknown},
title = {{Oligodendrocytes} regulate the adhesion molecule {ICAM}-1 in neuroinflammation},
year = {2021}
}
@article{faucris.119490624,
abstract = {In the adult mammalian hippocampus, new neurons are constantly added to the dentate gyrus. Adult neurogenesis is impaired in several neurodegenerative mouse models including ?-synuclein (a-syn) transgenic mice. Among different a-syn species, a-syn oligomers were reported to be the most toxic species for neurons. Here, we studied the impact of wild-type vs. oligomer-prone a-syn on neurogenesis. We compared the wild-type a-syn transgenic mouse model (Thy1-WTS) to its equivalent transgenic for oligomer-prone E57K-mutant a-syn (Thy1-E57K). Transgenic a-syn was highly expressed within the hippocampus of both models, but was not present within adult neural stem cells and neuroblasts. Proliferation and survival of newly generated neurons were unchanged in both transgenic models. Thy1-WTS showed a minor integration deficit regarding mushroom spine density of newborn neurons, whereas Thy1-E57K exhibited a severe reduction of all spines. We conclude that cell-extrinsic a-syn impairs mushroom spine formation of adult newborn neurons and that oligomer-prone a-syn exacerbates this integration deficit. Moreover, our data suggest that a-syn reduces the survival of newborn neurons by a cell-intrinsic mechanism during the early neuroblast development. The finding of increased spine pathology in Thy1-E57K is a new pathogenic function of oligomeric a-syn and precedes overt neurodegeneration. Thus, it may constitute a readout for therapeutic approaches.},
author = {Regensburger, Martin and Schreglmann, Sebastian R. and Stoll, Svenja and Rockenstein, Edward and Loskarn, Sandra and Xiang, Wei and Masliah, Eliezer and Winner, Beate},
doi = {10.1007/s00429-017-1561-5},
faupublication = {yes},
journal = {Brain Structure & Function},
note = {EVALuna2:4766},
peerreviewed = {Yes},
title = {{Oligomer}-prone {E57K}-mutant alpha-synuclein exacerbates integration deficit of adult hippocampal newborn neurons in transgenic mice},
year = {2017}
}
@article{faucris.267084107,
abstract = {Objective To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged >= 85 years. Methods Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged >= 85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. Results In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged >= 85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged >= 85 (HR >= 85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%-CI [0.66, 0.95]) in simple (p(interaction) = 0.129), adjusted (p(interaction) = 0.094) or weighted (p(interaction) = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged >= 85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). Interpretation The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2021},
author = {Polymeris, Alexandros A. and Macha, Kosmas and Paciaroni, Maurizio and Wilson, Duncan and Koga, Masatoshi and Cappellari, Manuel and Schaedelin, Sabine and Zietz, Annaelle and Peters, Nils and Seiffge, David J. and Haupenthal, David and Gaßmann, Luise and De Marchis, Gian Marco and Wang, Ruihao and Gensicke, Henrik and Stoll, Svenja and Thilemann, Sebastian and Avramiotis, Nikolaos S. and Bonetti, Bruno and Tsivgoulis, Georgios and Ambler, Gareth and Alberti, Andrea and Yoshimura, Sohei and Brown, Martin M. and Shiozawa, Masayuki and Lip, Gregory Y. H. and Venti, Michele and Acciarresi, Monica and Tanaka, Kanta and Mosconi, Maria Giulia and Takagi, Masahito and Jager, Rolf H. and Muir, Keith and Inoue, Manabu and Schwab, Stefan and Bonati, Leo H. and Lyrer, Philippe A. and Toyoda, Kazunori and Caso, Valeria and Werring, David J. and Kallmünzer, Bernd and Engelter, Stefan T.},
doi = {10.1002/ana.26267},
faupublication = {yes},
journal = {Annals of Neurology},
note = {CRIS-Team WoS Importer:2021-12-10},
peerreviewed = {Yes},
title = {{Oral} {Anticoagulants} in the {Oldest} {Old} with {Recent} {Stroke} and {Atrial} {Fibrillation}},
year = {2021}
}
@article{faucris.293825631,
author = {Tietze, Rainer and Unterweger, Harald and Janko, Christina and Civelek, Mehtap and Cicha, Iwona and Spielvogel, Helmut and Alexiou, Christoph},
doi = {10.2217/nnm-2022-0324},
faupublication = {yes},
journal = {Nanomedicine},
note = {CRIS-Team WoS Importer:2023-03-24},
peerreviewed = {unknown},
title = {{Orally} administered nanoparticles for gastrointestinal applications},
year = {2023}
}
@article{faucris.276878960,
abstract = {We are entering an era of medicine where increasingly sophisticated data will be obtained from patients to determine proper diagnosis, predict outcomes and direct therapies. We predict that the most valuable data will be produced by systems that are highly dynamic in both time and space. Three-dimensional (3D) organoids are poised to be such a highly valuable system for a variety of gastrointestinal (GI) diseases. In the lab, organoids have emerged as powerful systems to model molecular and cellular processes orchestrating natural and pathophysiological human tissue formation in remarkable detail. Preclinical studies have impressively demonstrated that these organs-in-a-dish can be used to model immunological, neoplastic, metabolic or infectious GI disorders by taking advantage of patient-derived material. Technological breakthroughs now allow to study cellular communication and molecular mechanisms of interorgan cross-talk in health and disease including communication along for example, the gut-brain axis or gut-liver axis. Despite considerable success in culturing classical 3D organoids from various parts of the GI tract, some challenges remain to develop these systems to best help patients. Novel platforms such as organ-on-a-chip, engineered biomimetic systems including engineered organoids, micromanufacturing, bioprinting and enhanced rigour and reproducibility will open improved avenues for tissue engineering, as well as regenerative and personalised medicine. This review will highlight some of the established methods and also some exciting novel perspectives on organoids in the fields of gastroenterology. At present, this field is poised to move forward and impact many currently intractable GI diseases in the form of novel diagnostics and therapeutics.},
author = {Günther, Claudia and Winner, Beate and Neurath, Markus and Stappenbeck, Thaddeus S.},
doi = {10.1136/gutjnl-2021-326560},
faupublication = {yes},
journal = {Gut},
keywords = {gastrointestinal pathology; gastrointestinal physiology; intestinal stem cell; stem cells},
note = {CRIS-Team WoS Importer:2022-06-17},
peerreviewed = {Yes},
title = {{Organoids} in gastrointestinal diseases: from experimental models to clinical translation},
url = {https://gut.bmj.com/content/early/2022/05/30/gutjnl-2021-326560},
year = {2022}
}
@article{faucris.209898369,
abstract = {BACKGROUND: Small fiber neuropathy (SFN) is a severe and disabling chronic pain syndrome with no causal and limited symptomatic treatment options. Mechanistically based individual treatment is not available. We report an in-vitro predicted individualized treatment success in one therapy-refractory Caucasian patient suffering from SFN for over ten years.
METHODS: Intrinsic excitability of human induced pluripotent stem cell (iPSC) derived nociceptors from this patient and respective controls were recorded on multi-electrode (MEA) arrays, in the presence and absence of lacosamide. The patient's pain ratings were assessed by a visual analogue scale (10: worst pain, 0: no pain) and treatment effect was objectified by microneurography recordings of the patient's single nerve C-fibers.
FINDINGS: We identified patient-specific changes in iPSC-derived nociceptor excitability in MEA recordings, which were reverted by the FDA-approved compound lacosamide in vitro. Using this drug for individualized treatment of this patient, the patient's pain ratings decreased from 7.5 to 1.5. Consistent with the pain relief reported by the patient, microneurography recordings of the patient's single nerve fibers mirrored a reduced spontaneous nociceptor (C-fiber) activity in the patient during lacosamide treatment. Microneurography recordings yielded an objective measurement of altered peripheral nociceptor activity following treatment.
INTERPRETATION: Thus, we are here presenting one example of successful patient specific precision medicine using iPSC technology and individualized therapeutic treatment based on patient-derived sensory neurons.},
author = {Namer, Barbara and Schmidt, Diana and Eberhardt, Esther and Maroni, Michele and Dorfmeister, Eva and Kleggetveit, Inge Petter and Kaluza, Luisa and Meents, Jannis and Gerlach, Aaron and Lin, Zhixin and Winterpacht, Andreas and Dragicevic, Elena and Kohl, Zacharias and Schüttler, Jürgen and Kurth, Ingo and Warncke, Torhild and Jorum, Ellen and Winner, Beate and Lampert, Angelika},
doi = {10.1016/j.ebiom.2018.11.042},
faupublication = {yes},
journal = {EBioMedicine},
note = {EVALuna2:35119},
peerreviewed = {Yes},
title = {{Pain} relief in a neuropathy patient by lacosamide: {Proof} of principle of clinical translation from patient-specific {iPS} cell-derived nociceptors},
year = {2018}
}
@article{faucris.119564984,
author = {Moessner, Rotraut and Frambach, Yvonne and Wilsmann-Theis, Dagmar and Loehr, Sabine and Jacobi, Arnd and Weyergraf, Ansgar and Mueller, Michael and Philipp, Sandra and Renner, Regina and Traupe, Heiko and Burkhardt, Harald and Kingo, Kuelli and Koks, Sulev and Uebe, Steffen and Sticherling, Michael and Sticht, Heinrich and Oji, Vinzenz and Hüffmeier, Ulrike},
doi = {10.1038/jid.2015.186},
faupublication = {yes},
journal = {Journal of Investigative Dermatology},
note = {EVALuna2:9269},
pages = {2538-41},
peerreviewed = {Yes},
title = {{Palmoplantar} {Pustular} {Psoriasis} {Is} {Associated} with {Missense} {Variants} in {CARD14}, but {Not} with {Loss}-of-{Function} {Mutations} in {IL36RN} in {European} {Patients}},
volume = {135},
year = {2015}
}
@article{faucris.123519484,
abstract = {Alcohol is a widely consumed drug that can lead to addiction and severe brain damage. However, alcohol is also used as self-medication for psychiatric problems, such as depression, frequently resulting in depression-alcoholism comorbidity. Here, we identify the first molecular mechanism for alcohol use with the goal to self-medicate and ameliorate the behavioral symptoms of a genetically induced innate depression. An induced over-expression of acid sphingomyelinase (ASM), as was observed in depressed patients, enhanced the consumption of alcohol in a mouse model of depression. ASM hyperactivity facilitates the establishment of the conditioned behavioral effects of alcohol, and thus drug memories. Opposite effects on drinking and alcohol reward learning were observed in animals with reduced ASM function. Importantly, free-choice alcohol drinking-but not forced alcohol exposure-reduces depression-like behavior selectively in depressed animals through the normalization of brain ASM activity. No such effects were observed in normal mice. ASM hyperactivity caused sphingolipid and subsequent monoamine transmitter hypo-activity in the brain. Free-choice alcohol drinking restores nucleus accumbens sphingolipid- and monoamine homeostasis selectively in depressed mice. A gene expression analysis suggested strong control of ASM on the expression of genes related to the regulation of pH, ion transmembrane transport, behavioral fear response, neuroprotection and neuropeptide signaling pathways. These findings suggest that the paradoxical antidepressant effects of alcohol in depressed organisms are mediated by ASM and its control of sphingolipid homeostasis. Both emerge as a new treatment target specifically for depression-induced alcoholism.},
author = {Müller, Christiane and Kalinichenko, Liubov and Tiesel, Jens and Witt, Matthias and Stöckl, Thomas and Sprenger, Eva and Fuchser, Jens and Beckmann, Janine and Praetner, Marc and Huber, Sabine and Amato, Davide and Mühle, Christiane and Büttner, Christian and Ekici, Arif Bülent and Smaga, Irena and Pomierny-Chamiolo, Lucyna and Pomierny, Bartosz and Filip, Malgorzata and Eulenburg, Volker and Gulbins, Erich and Lourdusamy, Anbarasu and Reichel, Martin and Kornhuber, Johannes},
doi = {10.1007/s00401-016-1658-6},
faupublication = {yes},
journal = {Acta Neuropathologica},
note = {EVALuna2:3919},
peerreviewed = {Yes},
title = {{Paradoxical} antidepressant effects of alcohol are related to acid sphingomyelinase and its control of sphingolipid homeostasis},
year = {2016}
}
@article{faucris.292086303,
abstract = {Background:Due to the absence of robust biomarkers, and the low sensitivity and specificity of routine imaging techniques, the differential diagnosis between Parkinson's disease (PD) and multiple system atrophy (MSA) is challenging. High-field magnetic resonance imaging (MRI) opened up new possibilities regarding the analysis of pathological alterations associated with neurodegenerative processes. Recently, we have shown that quantitative susceptibility mapping (QSM) enables visualization and quantification of two major histopathologic hallmarks observed in MSA: reduced myelin density and iron accumulation in the basal ganglia of a transgenic murine model of MSA. It is therefore emerging as a promising imaging modality on the differential diagnosis of Parkinsonian syndromes. Objectives:To assess QSM on high-field MRI for the differential diagnosis of PD and MSA. Methods:We assessed 23 patients (nine PDs and 14 MSAs) and nine controls using QSM on 3T and 7T MRI scanners at two academic centers. Results:We observed increased susceptibility in MSA at 3T in prototypical subcortical and brainstem regions. Susceptibility measures of putamen, pallidum, and substantia nigra reached excellent diagnostic accuracy to separate both synucleinopathies. Increase toward 100% sensitivity and specificity was achieved using 7T MRI in a subset of patients. Magnetic susceptibility correlated with age in all groups, but not with disease duration in MSA. Sensitivity and specificity were particularly high for possible MSA, and reached 100% in the putamen. Conclusion:Putaminal susceptibility measures, in particular on ultra-high-field MRI, may distinguish MSA patients from both, PD and controls, allowing an early and sensitive diagnosis of MSA.},
author = {Marxreiter, Franz and Lambrecht, Vera and Mennecke, Angelika and Hanspach, Jannis and Jukic, Jelena and Regensburger, Martin and Herrler, Jürgen and German, Alexander and Kassubek, Jan and Groen, Georg and Mueller, Hans-Peter and Laun, Frederik Bernd and Dörfler, Arnd and Winkler, Jürgen and Schmidt, Manuel},
doi = {10.1177/17562864221143834},
faupublication = {yes},
journal = {Therapeutic Advances in Neurological Disorders},
month = {Jan},
note = {CRIS-Team WoS Importer:2023-03-17},
peerreviewed = {Yes},
title = {{Parkinson}'s disease or multiple system atrophy: potential separation by quantitative susceptibility mapping},
volume = {16},
year = {2023}
}
@article{faucris.302902148,
abstract = {Pathogenic heterozygous variants in SCN2A, which encodes the neuronal sodium channel Na(V)1.2, cause different types of epilepsy or intellectual disability (ID)/autism without seizures. Previous studies using mouse models or heterologous systems suggest that Na(V)1.2 channel gain-of-function typically causes epilepsy, whereas loss-of-function leads to ID/autism. How altered channel biophysics translate into patient neurons remains unknown. Here, we investigated iPSC-derived early-stage cortical neurons from ID patients harboring diverse pathogenic SCN2A variants [p.(Leu611Valfs*35); p.(Arg937Cys); p.(Trp1716*)] and compared them with neurons from an epileptic encephalopathy (EE) patient [p.(Glu1803Gly)] and controls. ID neurons consistently expressed lower Na(V)1.2 protein levels. In neurons with the frameshift variant, Na(V)1.2 mRNA and protein levels were reduced by similar to 50%, suggesting nonsense-mediated decay and haploinsufficiency. In other ID neurons, only protein levels were reduced implying Na(V)1.2 instability. Electrophysiological analysis revealed decreased sodium current density and impaired action potential (AP) firing in ID neurons, consistent with reduced Na(V)1.2 levels. In contrast, epilepsy neurons displayed no change in Na(V)1.2 levels or sodium current density, but impaired sodium channel inactivation. Single-cell transcriptomics identified dysregulation of distinct molecular pathways including inhibition of oxidative phosphorylation in neurons with SCN2A haploinsufficiency and activation of calcium signaling and neurotransmission in epilepsy neurons. Together, our patient iPSC-derived neurons reveal characteristic sodium channel dysfunction consistent with biophysical changes previously observed in heterologous systems. Additionally, our model links the channel dysfunction in ID to reduced Na(V)1.2 levels and uncovers impaired AP firing in early-stage neurons. The altered molecular pathways may reflect a homeostatic response to Na(V)1.2 dysfunction and can guide further investigations.},
author = {Asadollahi, Reza and Delvendahl, and Muff, R. and Tan, G. and Rodrieguez, D. G. and Turan, Sören and Russo, M. and Oneda, B. and Joset, P. and Boonsawat, P. and Masood, R. and Mocera, M. and Ivanovski, I. and Baumer, A. and Bachmann-Gagescu, R. and Schlapbach, Ralph and Rehrauer, H. and Steindl, K. and Begemann, A. and Reis, André and Winkler, Jürgen and Winner, Beate and Mueller, M. and Rauch, A.},
doi = {10.1093/hmg/ddad048},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {CRIS-Team WoS Importer:2023-05-26},
peerreviewed = {Yes},
title = {{Pathogenic} {SCN2A} variants cause early-stage dysfunction in patient-derived neurons},
year = {2023}
}
@article{faucris.307360452,
abstract = {Patients with Systemic Lupus Erythematosus (SLE) carry an increased risk for the development of coronary artery disease (CAD). The R131 allele of the Fc gamma receptor IIa (FcγRIIa) is associated with SLE incidence and disease severity but also with CAD. Compared to stable angina pectoris (SAP) the unstable angina (UAP), as a manifestation of destabilizing CAD, is associated with increased risk of persistent instability, myocardial infarction, and death. Identification of clinically relevant determinants for unstable angina promises reduction of UAP-associated mortality in patients with SLE. We conducted a clinical study among 553 consecutive patients with stable angina pectoris (n 330) and unstable angina pectoris (n 223). All patients were genotyped for a frequent functional variant at position 131 of the mature FcγRIIa. UAP, but not SAP was significantly associated with the R/R131 genotype (P < 0.001). In troponin-negative patients with angina carrying the R/R131 genotype the odds ratio for suffering from UAP was 4.02 (95% confidence interval, 2.526.41) compared to those with non-R/R131 genotypes. In a multivariable analysis, the R/R131 genotype independently predicted the risk for development of UAP in a model adjusted for classical atherogenic risk factors. Our data imply that risk stratification of SLE- and other high risk patients with troponin-negative angina could be significantly improved by FcγRIIa genotyping. © Informa UK, Ltd.},
author = {Raaz-Schrauder, Dorette and Ekici, Arif Bülent and Munoz, Luis Enrique and Klinghammer, Lutz and Voll, Reinhard E. and Leusen, Jeanette H.W. and Van De Winkel, Jan G.J. and Reis, André and Schett, Georg and Garlichs, Christoph and Herrmann, Martin},
doi = {10.3109/08916934.2012.682665},
faupublication = {yes},
journal = {Autoimmunity},
keywords = {Allele R131; Coronary disease; Fc gamma receptor IIa; SLE; Stable; Unstable angina pectoris},
note = {CRIS-Team Scopus Importer:2023-07-10},
pages = {556-564},
peerreviewed = {Yes},
title = {{Patients} with unstable angina pectoris show an increased frequency of the {Fc} gamma {RIIa} {R131} allele},
volume = {45},
year = {2012}
}
@article{faucris.121887084,
abstract = {Human pluripotent stem cells (hPSCs) offer the opportunity to generate neuronal cells, including nociceptors. Using a chemical-based approach, we generated nociceptive sensory neurons from HUES6 embryonic stem cells and retrovirally reprogrammed induced hPSCs derived from fibroblasts. The nociceptive neurons expressed respective markers and showed tetrodotoxin-sensitive (TTXs) and -resistant (TTXr) voltage-gated sodium currents in patch-clamp experiments. In contrast to their counterparts from rodent dorsal root ganglia, TTXr currents of hPSC-derived nociceptors unexpectedly displayed a significantly more hyperpolarized voltage dependence of activation and fast inactivation. This apparent discrepancy is most likely due to a substantial expression of the developmentally important sodium channel NAV1.5. In view of the obstacles to recapitulate neuropathic pain in animal models, our data advance hPSC-derived nociceptors as a better model to study developmental and pathogenetic processes in human nociceptive neurons and to develop more specific small molecules to attenuate pain.},
author = {Eberhardt, Esther and Havlicek, Steven and Schmidt, Diana and Link, Andrea and Neacsu, Cristian and Kohl, Zacharias and Hampl, Martin and Kist, Andreas and Klinger, Alexandra and Nau, Carla and Schüttler, Jürgen and Alzheimer, Christian and Winkler, Jürgen and Namer, Barbara and Winner, Beate and Lampert, Angelika},
doi = {10.1016/j.stemcr.2015.07.010},
faupublication = {yes},
journal = {Stem Cell Reports},
note = {EVALuna2:2465},
pages = {305-13},
peerreviewed = {Yes},
title = {{Pattern} of {Functional} {TTX}-{Resistant} {Sodium} {Channels} {Reveals} a {Developmental} {Stage} of {Human} {iPSC}- and {ESC}-{Derived} {Nociceptors}},
volume = {5},
year = {2015}
}
@article{faucris.124196644,
abstract = {Objective. To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively. Methods. We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR. Results. Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes. Conclusions. PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation.},
author = {Klinger, Patricia and Lukassen, Sören and Ferrazzi, Fulvia and Ekici, Arif Bülent and Hotfiel, Thilo and Swoboda, Bernd and Aigner, T. and Gelse, Kolja},
doi = {10.1155/2017/7183516},
faupublication = {yes},
journal = {BioMed Research International},
note = {EVALuna2:9364},
pages = {7183516},
peerreviewed = {Yes},
title = {{PEDF} {Is} {Associated} with the {Termination} of {Chondrocyte} {Phenotype} and {Catabolism} of {Cartilage} {Tissue}},
volume = {2017},
year = {2017}
}
@inproceedings{faucris.248099498,
address = {LONDON},
author = {Kallmünzer, Bernd and Macha, Kosmas and Wang, Ruihao and Siedler, Gabriela and Stoll, Svenja and Marsch, Armin and Gerner, Stefan and Winder, Klemens and Koehn, J. and Schwab, Stefan and Koehrmann, M.},
booktitle = {INTERNATIONAL JOURNAL OF STROKE},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {183-183},
peerreviewed = {unknown},
publisher = {SAGE PUBLICATIONS LTD},
title = {{PERIPHERAL} {PULSE} {MEASUREMENTS} {FOR} {THE} {DETECTION} {OF} {SILENT} {ATRIAL} {FIBRILLATION}: {RESULTS} {FROM} {THE} {PROSPECTIVE}, {CONTROLLED} {TRIAL} "{KNOW} {YOUR} {PULSE} {POST} {STROKE}"},
year = {2020}
}
@article{faucris.207824268,
abstract = {PURPOSE: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.
METHODS: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.
RESULTS: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.
CONCLUSION: Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.},
author = {Ivanovski, Ivan and Djuric, Olivera and Caraffi, Stefano Giuseppe and Santodirocco, Daniela and Pollazzon, Marzia and Rosato, Simonetta and Cordelli, Duccio Maria and Abdalla, Ebtesam and Accorsi, Patrizia and Adam, Margaret P. and Ajmone, Paola Francesca and Badura-Stronka, Magdalena and Baldo, Chiara and Baldi, Maddalena and Bayat, Allan and Bigoni, Stefania and Bonvicini, Federico and Breckpot, Jeroen and Callewaert, Bert and Cocchi, Guido and Cuturilo, Goran and De Brasi, Daniele and Devriendt, Koenraad and Dinulos, Mary Beth and Hjortshoj, Tina Duelund and Epifanio, Roberta and Faravelli, Francesca and Fiumara, Agata and Formisano, Debora and Giordano, Lucio and Grasso, Marina and Gronborg, Sabine and Iodice, Alessandro and Iughetti, Lorenzo and Kuburovic, Vladimir and Kutkowska-Kazmierczak, Anna and Lacombe, Didier and Lo Rizzo, Caterina and Luchetti, Anna and Malbora, Baris and Mammi, Isabella and Mari, Francesca and Montorsi, Giulia and Moutton, Sebastien and Moller, Rikke S. and Muschke, Petra and Nielsen, Jens Erik Klint and Obersztyn, Ewa and Pantaleoni, Chiara and Pellicciari, Alessandro and Pisanti, Maria Antonietta and Prpic, Igor and Poch-Olive, Maria Luisa and Raviglione, Federico and Renieri, Alessandra and Ricci, Emilia and Rivieri, Francesca and Santen, Gijs W. and Savasta, Salvatore and Scarano, Gioacchino and Schanze, Ina and Selicorni, Angelo and Silengo, Margherita and Smigiel, Robert and Spaccini, Luigina and Sorge, Giovanni and Szczaluba, Krzysztof and Tarani, Luigi and Tone, Luis Gonzaga and Toutain, Annick and Trimouille, Aurelien and Valera, Elvis Terci and Vergano, Samantha Schrier and Zanotta, Nicoletta and Zenker, Martin and Conidi, Andrea and Zollino, Marcella and Rauch, Anita and Zweier, Christiane and Garavelli, Livia},
doi = {10.1038/gim.2017.221},
faupublication = {yes},
journal = {Genetics in Medicine},
note = {EVALuna2:34827},
pages = {965-975},
peerreviewed = {Yes},
title = {{Phenotype} and genotype of 87 patients with {Mowat}-{Wilson} syndrome and recommendations for care},
volume = {20},
year = {2018}
}
@inproceedings{faucris.207338255,
author = {Furtmair, R. and Kühn, Charlotte and Koenig, C. and Ekici, Arif Bülent and Klinghammer, Lutz and Achenbach, Stephan and Reis, André and Tauchi, M. and Dietel, B.},
faupublication = {yes},
note = {EVALuna2:33679},
pages = {E78-E78},
peerreviewed = {Yes},
title = {{PHENOTYPE} {OF} {VULNERABLE} {ATHEROSCLEROTIC} {PLAQUES} {SHOWS} {STRONG} {ASSOCIATION} {WITH} {SINGLE} {NUCLEOTIDE} {POLYMORPHISM} {ALLELES} {OF} {COMMON} {RISK} {VARIANTS} {FOR} {CORONARY} {ARTERY} {DISEASE}},
volume = {252},
year = {2016}
}
@article{faucris.119626364,
abstract = {Mutations in the Dynamin 2 gene (DNM2) cause autosomal dominant centronuclear myopathy or autosomal dominant (AD) Charcot-Marie-Tooth (CMT) disease. Here the authors report one large Czech family with 15 members affected with an AD CMT phenotype of extraordinary variability. Genetic linkage analysis using SNP arrays revealed a locus of about 9.6 Mb on chromosome 19p13.1-13.2. In this critical interval, 373 genes were located. The only gene herein known to be associated with an intermediate type of CMT was Dynamin 2 (DNM2). Subsequent sequence analysis of the DNM2 gene in the index patient revealed a novel missense mutation p.Met580Thr. This missense mutation segregated with the neuropathy, indicating the causal character of this mutation. The phenotype of CMT in this family shows mild to moderate impairment with relatively preserved upper limbs and a very broad range of the onset of clinical symptoms from an early onset around the age of 12 to the late onset during the fifth decade. Electrophysiology showed an intermediate type of peripheral neuropathy. The motor median nerve conduction velocity varied from 36 m/s to normal values with signs of asymmetrical affection of peripheral nerves. No additional symptoms such as cranial nerve involvement, cataract, and signs of neutropenia or myopathy syndrome were observed in any member of the family yet. The progression was slow with no loss of ambulation. The authors suggest that the characterization of clinical variability in a single family may help to direct the genetic analysis directly to the rarely observed DNM2 mutations.},
author = {Haberlova, J. and Mazanec, R. and Ridzon, P. and Barankova, L. and Nuernberg, G. and Nuernberg, P. and Sticht, Heinrich and Hühne, Kathrin and Seeman, P. and Rautenstrauss, Bernd},
doi = {10.3109/01677063.2011.627484},
faupublication = {yes},
journal = {Journal of Neurogenetics},
note = {EVALuna2:26266},
pages = {182-8},
peerreviewed = {Yes},
title = {{Phenotypic} variability in a large {Czech} family with a {Dynamin} 2-associated {Charcot}-{Marie}-{Tooth} neuropathy},
volume = {25},
year = {2011}
}
@article{faucris.211781496,
abstract = {SOX11 is a key Transcription Factor (TF) in the regulation of embryonic and adult neurogenesis, whose mutation has recently been linked to an intellectual disability syndrome in humans. SOX11's transient activity during neurogenesis is critical to ensure the precise execution of the neurogenic program. Here, we report that SOX11 displays differential subcellular localizations during the course of neurogenesis. Western-Blot analysis of embryonic mouse brain lysates indicated that SOX11 is post-translationally modified by phosphorylation. Using Mass Spectrometry, we found 10 serine residues in the SOX11 protein that are putatively phosphorylated. Systematic analysis of phospho-mutant SOX11 resulted in the identification of the S30 residue, whose phosphorylation promotes nuclear over cytoplasmic localization of SOX11. Collectively, these findings uncover phosphorylation as a novel layer of regulation of the intellectual disability gene Sox11.},
author = {Balta, Elli-Anna and Wittmann, Marie-Theres and Jung, Matthias and Sock, Elisabeth and Häberle, Benjamin and Heim, Birgit and Von Zweydorf, Felix and Heppt, Jana and von Wittgenstein, Julia and Gloeckner, Christian Johannes and Lie, Dieter Chichung},
doi = {10.3389/fnmol.2018.00211},
faupublication = {yes},
journal = {Frontiers in Molecular Neuroscience},
note = {EVALuna2:35742},
peerreviewed = {Yes},
title = {{Phosphorylation} {Modulates} the {Subcellular} {Localization} of {SOX11}},
volume = {11},
year = {2018}
}
@article{faucris.211781726,
abstract = {The intellectual disability gene, Sox11, encodes for a critical neurodevelopmental transcription factor with functions in precursor survival, neuronal fate determination, migration and morphogenesis. The mechanisms regulating SOX11's activity remain largely unknown. Mass spectrometric analysis uncovered that SOX11 can be post-translationally modified by phosphorylation. Here, we report that phosphorylatable serines surrounding the high-mobility group box modulate SOX11's transcriptional activity. Through Mass Spectrometry (MS), co-immunoprecipitation assays and in vitro phosphorylation assays followed by MS we verified that protein kinase A (PKA) interacts with SOX11 and phosphorylates it on S133. In vivo replacement of SoxC factors in developing adult-generated hippocampal neurons with SOX11 S133 phospho-mutants indicated that phosphorylation on S133 modulates dendrite development of adult-born dentate granule neurons, while reporter assays suggested that S133 phosphorylation fine-tunes the activation of select target genes. These data provide novel insight into the control of the critical neurodevelopmental regulator SOX11 and imply SOX11 as a mediator of PKA-regulated neuronal development.},
author = {Balta, Elli-Anna and Schäffner, Iris and Wittmann, Marie-Theres and Sock, Elisabeth and Von Zweydorf, Felix and von Wittgenstein, Julia and Steib, Kathrin and Heim, Birgit and Kremmer, Elisabeth and Häberle, Benjamin and Ueffing, Marius and Lie, Dieter Chichung and Gloeckner, Christian Johannes},
doi = {10.1038/s41598-018-34480-x},
faupublication = {yes},
journal = {Scientific Reports},
note = {EVALuna2:35738},
peerreviewed = {Yes},
title = {{Phosphorylation} of the neurogenic transcription factor {SOX11} on serine 133 modulates neuronal morphogenesis},
volume = {8},
year = {2018}
}
@article{faucris.241999395,
author = {Argente-Escrig, H. and Schultheis, D. and Kamm, L. and Schowalter, M. and Thiel, C. and Türk, M. and Clemen, C. S. and Muelas, N. and Castañón, M. J. and Wiche, G. and Herrmann, H. and Vilchez, J. J. and Schröder, Rolf},
doi = {10.1111/nan.12652},
faupublication = {yes},
journal = {Neuropathology and Applied Neurobiology},
note = {CRIS-Team Scopus Importer:2020-08-28},
peerreviewed = {Yes},
title = {{Plectin}-related scapuloperoneal myopathy with treatment-responsive myasthenic syndrome},
year = {2020}
}
@article{faucris.252783086,
abstract = {Most of our current knowledge about cellular phenotypes in neurodevelopmental and neurodegenerative diseases in humans was gathered from studies in postmortem brain tissues. These samples often represent the end-stage of the disease and therefore are not always a fair representation of how the disease developed. Moreover, under these circumstances, the pathology observed could be a secondary effect rather than the authentic disease cellular phenotype. Likewise, the rodent models available do not always recapitulate the pathology from human diseases. In this review, we will examine recent literature on the use of induced pluripotent stem cells to model neurodegenerative and neurodevelopmental diseases. We highlight the characteristics of diseases like spinal muscular atrophy and familial dysautonomia that allowed partial modeling of the disease phenotype. We review human stem cell literature on common neurodegenerative late-onset diseases such as Parkinson's disease and amyotrophic lateral sclerosis where patients' cells have been successfully reprogrammed but a disease phenotype has not yet been described. So far, the technique is of great interest for early onset monogenetic neurodevelopmental diseases. We speculate about potential further experimental requirements and settings for reprogrammed neurons for in vitro disease modeling and drug discovery.},
author = {Winner, Beate and Marchetto, Maria C. N. and Gage, Fred H.},
doi = {10.1093/hmg/ddq159},
faupublication = {no},
journal = {Human Molecular Genetics},
pages = {R71-6},
peerreviewed = {Yes},
title = {{Pluripotent} stem cells in neurodegenerative and neurodevelopmental diseases.},
volume = {19},
year = {2010}
}
@article{faucris.236506309,
abstract = {The physico-chemical characteristics of the extracellular matrix (ECM) cause mechanical cues that could elicit responses in the survival rate of cortical neuronal cells. Efficient neurite outgrowth in vitro, is critical for successful cultivation of cortical neuronal cells and the potential for attempts at regeneration of the central nervous system (CNS) in vivo. Relatively soft and hydrophilic, microbially synthesized aromatic polyester, polyhydroxyphenylvalerate (PHPV) was blended 50:50 with the stiff and hydrophobic polycaprolactone (PCL) and electrospun in microfibers for use in a 3D (CellCrown™) configuration and in a 2D coverslip coated configuration. This blend allows a 2.3-fold increase in the life-span of human induced pluripotent stem derived cortical neuronal cells (hiPS) compared to pure PCL fibers. HiPS-derived cortical neuronal cells grown on PHPV/PCL fibers show a 3.8-fold higher cumulative neurite elaboration compared to neurites grown on PCL fibers only. 96% of cortical neuronal cells die after 8 days of growth when plated on PCL fibers alone while >83% and 55% are alive on PHPV/PCL fibers on day 8 and day 17, respectively. An increased migration rate of cortical neuronal cells is also promoted by the blend compared to the PCL fibers alone. The critical survival rate improvement of hiPS derived cortical neuronal cells on PHPV/PCL blend holds promise in using these biocompatible nanofibers as implantable materials for regenerative purposes of an active cortical neuronal population after full maturation in vitro.},
author = {Cerrone, Federico and Pozner, Tatyana and Siddiqui, Aarif and Ceppi, Paolo and Winner, Beate and Rajendiran, Murugan and Babu, Ramesh and Ibrahim, Hossam S. and Rodriguez, Brian J. and Winkler, Jürgen and Murphy, Keith J. and O'Connor, Kevin E.},
doi = {10.1016/j.msec.2020.110832},
faupublication = {yes},
journal = {Materials Science and Engineering C},
keywords = {Cortical neurons; Electrospinning; HiPSC; Mechanoresponse; Neuroregeneration; Polyhydroxyalkanoates},
note = {CRIS-Team Scopus Importer:2020-03-27},
peerreviewed = {Yes},
title = {{Polyhydroxyphenylvalerate}/polycaprolactone nanofibers improve the life-span and mechanoresponse of human {IPSC}-derived cortical neuronal cells},
volume = {111},
year = {2020}
}
@article{faucris.120811064,
abstract = {Alternative mRNA splicing coupled to nonsense-mediated decay (NMD) is a common mRNA surveillance pathway also known to dynamically modulate gene expression in response to cellular stress. Here, we investigated the involvement of this pathway in the regulation of lysyl oxidase-like 1 (LOXL1) expression in response to pseudoexfoliation (PEX)-associated pathophysiologic factors.Transcript levels of LOXL1 isoforms were determined in ocular tissues obtained from donor eyes without and with PEX syndrome. Pseudoexfoliation-relevant cell types, including human Tenon's capsule fibroblasts (hTCF) and trabecular meshwork cells (hTMC), were exposed to puromycin, caffeine, TGF-?1, homocysteine, IL-6, retinoic acid, UV-B radiation, oxidative stress, and mechanical stress for up to 48 hours. Western blot analysis was carried out using antibodies against LOXL1, (phosphorylated-) eukaryotic initiation factor 2-? (eIF2-?), and regulator of nonsense transcripts 2 (UPF2). RNA interference was used to knockdown UPF1-3 and Serine/threonine-protein kinase (SMG1).Constitutive expression of wild-type LOXL1 and alternatively spliced LOXL1-a transcripts was detected in all ocular tissues showing highest levels in trabecular meshwork and differential expression between PEX and control specimens. LOXL1-a transcripts were upregulated in hTCF and hTMC by NMD inhibitors puromycin and caffeine (>=6-fold; P < 0.01) or after knockdown of NMD core factors (>=2-fold; P < 0.05), whereas mRNA and protein levels of LOXL1 were reduced (<=0.8 fold; P < 0.05). Exposure of cells to various PEX-associated (stress) factors, including TGF-?1, UV-B light, oxidative stress, mechanical stress, and retinoic acid enhanced LOXL1-a transcript levels (>=1.5-fold; P < 0.05), while partially downregulating LOXL1 levels (<=0.7-fold; P < 0.05). Stress-induced inhibition of NMD was dependent on phosphorylation of eIF2?.These findings provide evidence for a functional role of alternative splicing coupled to NMD in the posttranscriptional regulation of LOXL1 gene expression and suggest this mechanism to represent a dynamic mode of adapting LOXL1 expression to PEX-associated environmental and nutritional cues.},
author = {Berner, Daniel and Zenkel, Matthias and Pasutto, Francesca and Hoja, Ursula and Liravi, Panah and Gusek-Schneider, Gabriele C. and Kruse, Friedrich and Schödel, Johannes and Reis, André and Schlötzer-Schrehardt, Ursula},
doi = {10.1167/iovs.17-22963},
faupublication = {yes},
journal = {Investigative Ophthalmology & Visual Science},
note = {EVALuna2:9393},
pages = {5930-5940},
peerreviewed = {Yes},
title = {{Posttranscriptional} {Regulation} of {LOXL1} {Expression} {Via} {Alternative} {Splicing} and {Nonsense}-{Mediated} {mRNA} {Decay} as an {Adaptive} {Stress} {Response}},
volume = {58},
year = {2017}
}
@article{faucris.106486644,
abstract = {Alcohol use disorders are major psychiatric disorders. Correlational studies in humans suggested organizational hormonal effects during embryonic development as a risk factor for adult alcohol dependence. Permanent changes can be induced by the activity of sex hormones, like testosterone. Here, we demonstrate a relationship between prenatal androgen receptor (AR)-activation and adult alcohol as well as water drinking in mice in a sex-dependent fashion. Prenatal AR inhibition using the antagonist flutamide decreased adult male alcohol consumption. In contrast, prenatal AR activation by dihydrotestosterone (DHT) led to an increase in adult alcohol consumption in females. These effects were different in adult water drinking, flutamide increased water consumption in females and DHT increased water consumption in males. Prenatal flutamide reduced locomotion and anxiety in adult males but was ineffective in females. We found that prenatal AR activation controls adult levels of monoaminergic modulatory transmitters in the brain and blood hormone levels in a sex-specific way. RNA-Seq analysis confirmed a prenatal AR mediated control of adult expression of alcohol drinking-related genes like Bdnf and Per2. These findings demonstrate that prenatal androgen activity is a risk factor for the establishment of alcohol consumption in adults by its organizational effects.},
author = {Huber, Sabine and Zoicas, Iulia and Reichel, Martin and Mühle, Christiane and Büttner, Christian and Ekici, Arif Bülent and Eulenburg, Volker and Lenz, Bernd and Kornhuber, Johannes and Müller, Christian P.},
doi = {10.1111/adb.12540},
faupublication = {yes},
journal = {Addiction Biology},
note = {EVALuna2:4035},
peerreviewed = {Yes},
title = {{Prenatal} androgen receptor activation determines adult alcohol and water drinking in a sex-specific way},
year = {2017}
}
@article{faucris.228842327,
abstract = {Objective 17q12 microdeletions containing HNF1B and intragenic variants within this gene are associated with variable developmental, endocrine, and renal anomalies, often already noted prenatally as hyperechogenic/cystic kidneys. Here, we describe prenatal and postnatal phenotypes of seven individuals with HNF1B aberrations and compare their clinical and genetic data to those of previous studies. Methods Prenatal sequencing and postnatal chromosomal microarray analysis were performed in seven individuals with renal and/or neurodevelopmental phenotypes. We evaluated HNF1B-related clinical features from 82 studies and reclassified 192 reported intragenic HNF1B variants. Results In a prenatal case, we identified a novel in-frame deletion p.(Gly239del) within the HNF1B DNA-binding domain, a mutational hot spot as demonstrated by spatial clustering analysis and high computational prediction scores. The six postnatally diagnosed individuals harbored 17q12 microdeletions. Literature screening revealed variable reporting of HNF1B-associated clinical traits. Overall, both mutation groups showed a high phenotypic heterogeneity. The reclassification of all previously reported intragenic HNF1B variants provided an up-to-date overview of the mutational spectrum. Conclusions We highlight the value of prenatal HNF1B screening in renal developmental diseases. Standardized clinical reporting and systematic classification of HNF1B variants are necessary for a more accurate risk quantification of prenatal and postnatal clinical features, improving genetic counseling and prenatal decision making.},
author = {Vasileiou, Georgia and Hoyer, Juliane and Thiel, Christian and Schaefer, Jan Thomas and Zapke, Maren and Krumbiegel, Mandy and Kraus, Cornelia and Zweier, Markus and Uebe, Steffen and Ekici, Arif Bülent and Schneider, Michael and Wiesener, Michael and Rauch, Anita and Faschingbauer, Florian and Reis, André and Zweier, Christiane and Popp, Bernt},
doi = {10.1002/pd.5556},
faupublication = {yes},
journal = {Prenatal Diagnosis},
note = {CRIS-Team WoS Importer:2019-11-08},
peerreviewed = {Yes},
title = {{Prenatal} diagnosis of {HNF1B}-associated renal cysts: {Is} there a need to differentiate intragenic variants from 17q12 microdeletion syndrome?},
year = {2019}
}
@article{faucris.216507824,
abstract = {IMPORTANCE Both primary and secondary forms of childhood glaucoma have many distinct causative mechanisms, and in many cases a cause is not immediately clear. The broad phenotypic spectrum of secondary glaucoma, particularly in individuals with variants in FOXC1 or PITX2 genes associated with Axenfeld-Rieger syndrome, makes it more difficult to diagnose patients with milder phenotypes. These cases are occasionally classified and managed as primary congenital glaucoma.},
author = {Siggs, Owen M. and Souzeau, Emmanuelle and Pasutto, Francesca and Dubowsky, Andrew and Smith, James E. H. and Taranath, Deepa and Pater, John and Rait, Julian L. and Narita, Andrew and Mauri, Lucia and Del Longo, Alessandra and Reis, André and Chappell, Angela and Kearns, Lisa S. and Staffieri, Sandra E. and Elder, James E. and Ruddle, Jonathan B. and Hewitt, Alex W. and Burdon, Kathryn P. and Mackey, David A. and Craig, Jamie E.},
doi = {10.1001/jamaophthalmol.2018.5646},
faupublication = {yes},
journal = {JAMA Ophthalmology},
note = {CRIS-Team WoS Importer:2019-04-25},
pages = {348-355},
peerreviewed = {unknown},
title = {{Prevalence} of {FOXC1} {Variants} in {Individuals} {With} a {Suspected} {Diagnosis} of {Primary} {Congenital} {Glaucoma}},
volume = {137},
year = {2019}
}
@article{faucris.282051845,
abstract = {Hereditary chronic kidney disease (CKD) appears to be more frequent than the clinical perception. Exome sequencing (ES) studies in CKD cohorts could identify pathogenic variants in similar to 10% of individuals. Tubulointerstitial kidney diseases, showing no typical clinical/histologic finding but tubulointerstitial fibrosis, are particularly difficult to diagnose. We used a targeted panel (29 genes) and MUC1-SNaPshot to sequence 271 DNAs, selected in defined disease entities and age cutoffs from 5217 individuals in the German Chronic Kidney Disease cohort. We identified 33 pathogenic variants. Of these 27 (81.8%) were in COL4A3/4/5, the largest group being 15 COL4A5 variants with nine unrelated individuals carrying c.1871G>A, p.(Gly624Asp). We found three cysteine variants in UMOD, a novel missense and a novel splice variant in HNF1B and the homoplastic MTTF variant m.616T>C. Copy-number analysis identified a heterozygous COL4A5 deletion, and a HNF1B duplication/deletion, respectively. Overall, pathogenic variants were present in 12.5% (34/271) and variants of unknown significance in 9.6% (26/271) of selected individuals. Bioinformatic predictions paired with gold standard diagnostics for MUC1 (SNaPshot) could not identify the typical cytosine duplication ("c.428dupC") in any individual, implying that ADTKD-MUC1 is rare. Our study shows that >10% of selected individuals carry disease-causing variants in genes partly associated with tubulointerstitial kidney diseases. COL4A3/4/5 genes constitute the largest fraction, implying they are regularly overlooked using clinical Alport syndrome criteria and displaying the existence of phenocopies. We identified variants easily missed by some ES pipelines. The clinical filtering criteria applied enriched for an underlying genetic disorder.},
author = {Popp, Bernt and Ekici, Arif Bülent and Knaup, Karl and Schneider, Karen and Uebe, Steffen and Park, Jonghun and Bafna, Vineet and Meiselbach, Heike and Eckardt, Kai-Uwe and Schiffer, Mario and Wiesmann da Silva Reis, André and Kraus, Cornelia and Wiesener, Michael},
doi = {10.1038/s41431-022-01177-9},
faupublication = {yes},
journal = {European Journal of Human Genetics},
note = {CRIS-Team WoS Importer:2022-09-23},
peerreviewed = {Yes},
title = {{Prevalence} of hereditary tubulointerstitial kidney diseases in the {German} {Chronic} {Kidney} {Disease} study},
year = {2022}
}
@article{faucris.280973706,
abstract = {Parkinson's disease (PD) as a progressive neurodegenerative disorder arises from multiple genetic and environmental factors. However, underlying pathological mechanisms remain poorly understood. Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) from sporadic PD (sPD) patients. Alterations in gene expression appear in pathways related to primary cilia (PC). Accordingly, in these hiPSC-derived hNPCs and neurons, we observe a shortening of PC. Additionally, we detect a shortening of PC in PINK1-deficient human cellular and mouse models of familial PD. Furthermore, in sPD models, the shortening of PC is accompanied by increased Sonic Hedgehog (SHH) signal transduction. Inhibition of this pathway rescues the alterations in PC morphology and mitochondrial dysfunction. Thus, increased SHH activity due to ciliary dysfunction may be required for the development of pathoetiological phenotypes observed in sPD like mitochondrial dysfunction. Inhibiting overactive SHH signaling may be a potential neuroprotective therapy for sPD.},
author = {Schmidt, Sebastian and Luecken, Malte D. and Truembach, Dietrich and Hembach, Sina and Niedermeier, Kristina M. and Wenck, Nicole and Pfluegler, Klaus and Stautner, Constantin and Boettcher, Anika and Lickert, Heiko and Ramirez-Suastegui, Ciro and Ahmad, Ruhel and Ziller, Michael J. and Fitzgerald, Julia C. and Ruf, Viktoria and Van De Berg, Wilma D. J. and Jonker, Allert J. and Gasser, Thomas and Winner, Beate and Winkler, Jürgen and Weisenhorn, Daniela M. Vogt and Giesert, Florian and Theis, Fabian J. and Wurst, Wolfgang},
doi = {10.1038/s41467-022-32229-9},
faupublication = {yes},
journal = {Nature Communications},
note = {CRIS-Team WoS Importer:2022-08-26},
peerreviewed = {Yes},
title = {{Primary} cilia and {SHH} signaling impairments in human and mouse models of {Parkinson}'s disease},
volume = {13},
year = {2022}
}
@inproceedings{faucris.207809552,
author = {Berner, Daniel and Pasutto, Francesca and Hoja, Ursula and Zenkel, Matthias and Ozaki, Mineo and Williams, Susan and Ramsay, Michele and Carmichael, Trevor R. and Kruse, Friedrich and Aung, Tin and Khor, Chiea Chuen and Reis, André and Schlötzer-Schrehardt, Ursula},
faupublication = {yes},
note = {EVALuna2:34734},
peerreviewed = {Yes},
title = {{Pseudoexfoliation} associated protective variant, rs7173049, reveals a novel regulatory region downstream of {LOXL1}},
volume = {59},
year = {2018}
}
@article{faucris.119336184,
abstract = {Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C>G transversion exerts a cis-acting effect on the expression levels of LOXL1, mediated by differential binding of the transcription factor RXR? (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1, eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression.},
author = {Pasutto, Francesca and Zenkel, Matthias and Hoja, Ursula and Berner, Daniel and Uebe, Steffen and Ferrazzi, Fulvia and Schoedel, Johannes and Liravi, Panah and Ozaki, Mineo and Paoli, Daniela and Frezzotti, Paolo and Mizoguchi, Takanori and Nakano, Satoko and Kubota, Toshiaki and Manabe, Shinichi and Salvi, Erika and Manunta, Paolo and Cusi, Daniele and Gieger, Christian and Wichmann, Heinz-Erich and Aung, Tin and Khor, Chiea Chuen and Kruse, Friedrich and Reis, André and Schlötzer-Schrehardt, Ursula},
doi = {10.1038/ncomms15466},
faupublication = {yes},
journal = {Nature Communications},
note = {EVALuna2:9367},
pages = {15466},
peerreviewed = {Yes},
title = {{Pseudoexfoliation} syndrome-associated genetic variants affect transcription factor binding and alternative splicing of {LOXL1}},
volume = {8},
year = {2017}
}
@article{faucris.109025004,
abstract = {Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA.A total of 15 single nucleotide polymorphisms were selected (PImmunochip <1×10(-4)) for validation genotyping in 1177 cases and 2155 controls using TaqMan. Meta-analysis of Immunochip and validation data sets consisted of 3139 PsA cases and 11 078 controls. Novel PsA susceptibility loci were compared with data from two large psoriasis studies (WTCCC2 and Immunochip) to determine PsA specificity.We found genome-wide significant association to rs2476601, mapping to PTPN22 (p=1.49×10(-9), OR=1.32), but no evidence for association in the psoriasis cohort (p=0.34) and the effect estimates were significantly different between PsA and psoriasis (p=3.2×10(-4)). Additionally, we found genome-wide significant association to the previously reported psoriasis risk loci; NOS2 (rs4795067, p=5.27×10(-9)).For the first time, we report genome-wide significant association of PTPN22 (rs2476601) to PsA susceptibility, but no evidence for association to psoriasis.},
author = {Bowes, John and Loehr, Sabine and Budu-Aggrey, Ashley and Uebe, Steffen and Bruce, Ian N. and Feletar, Marie and Marzo-Ortega, Helena and Helliwell, Philip and Ryan, Anthony W. and Kane, David and Korendowych, Eleanor and Alenius, Gerd-Marie and Giardina, Emiliano and Packham, Jonathan and Mcmanus, Ross and Fitzgerald, Oliver and Brown, Matthew A. and Behrens, Frank and Burkhardt, Harald and Mchugh, Neil and Hüffmeier, Ulrike and Ho, Pauline and Reis, André and Barton, Anne},
doi = {10.1136/annrheumdis-2014-207187},
faupublication = {yes},
journal = {Annals of the Rheumatic Diseases},
note = {EVALuna2:9275},
pages = {1882-5},
peerreviewed = {Yes},
title = {{PTPN22} is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further {PsA}-specific risk locus},
volume = {74},
year = {2015}
}
@inproceedings{faucris.228301014,
address = {LONDON},
author = {Hüffmeier, Ulrike and Sticht, Heinrich and Wenzel, J. and Wilsmann-Theis, D. and Wolff, K. and Löhr, Sabine and Frey, Benjamin and Hahn, M. and Ekici, Arif Bülent and Uebe, S. and Thiel, Christian and Wiesmann da Silva Reis, André and Prinz, J. and Oji, V. and Schulz, P. and Kingo, K. and Koks, S. and Moessner, R. and Munoz, Luis Enrique and Kremer, Andreas and Frey, Silke},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2019-06-15/2019-06-18},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {1366-1367},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{Rare} frameshift mutation in {SERPINA3} contributes to generalized pustular psoriasis},
venue = {Gothenburg, SWEDEN},
year = {2019}
}
@article{faucris.235418535,
author = {Frey, Silke and Sticht, Heinrich and Wilsmann-Theis, Dagmar and Gerschütz, Anne and Wolf, Katharina and Löhr, Sabine and Haskamp, Stefan and Frey, Benjamin and Hahn, Madelaine and Ekici, Arif Bülent and Uebe, Steffen and Thiel, Christian and Reis, André and Burkhardt, Harald and Behrens, Frank and Köhm, Michaela and Rech, Jürgen and Schett, Georg and Assmann, Gunter and Kingo, Külli and Kõks, Sulev and Mössner, Rotraut and Prinz, Jörg C. and Oji, Vinzenz and Schulz, Peter and Munoz, Luis Enrique and Kremer, Andreas and Wenzel, Jörg and Hüffmeier, Ulrike},
doi = {10.1016/j.jid.2019.11.024},
faupublication = {yes},
journal = {Journal of Investigative Dermatology},
note = {CRIS-Team Scopus Importer:2020-03-06},
peerreviewed = {Yes},
title = {{Rare} {Loss}-of-{Function} {Mutation} in {SERPINA3} in {Generalized} {Pustular} {Psoriasis}},
year = {2020}
}
@article{faucris.274825254,
abstract = {Parkinson disease (PD) is a neurodegenerative disorder characterized by
the abnormal intracellular accumulation of SNCA/α-synuclein. While the
exact mechanisms underlying SNCA pathology are not fully understood,
increasing evidence suggests the involvement of autophagy as well as
lysosomal deficiencies. Because CTSD (cathepsin D) has been proposed to
be the major lysosomal protease involved in SNCA degradation, its
deficiency has been linked to the presence of insoluble SNCA conformers
in the brain of mice and humans as well as to the transcellular
transmission of SNCA aggregates. We here postulate that SNCA degradation
can be enhanced by the application of the recombinant human proform of
CTSD (rHsCTSD). Our results reveal that rHsCTSD is efficiently
endocytosed by neuronal cells, correctly targeted to lysosomes and
matured to an enzymatically active protease. In dopaminergic neurons
derived from induced pluripotent stem cells (iPSC) of PD patients
harboring the A53T mutation within the SNCA gene, we confirm the
reduction of insoluble SNCA after treatment with rHsCTSD. Moreover, we
demonstrate a decrease of pathological SNCA conformers in the brain and
within primary neurons of a ctsd-deficient mouse model after
dosing with rHsCTSD. Boosting lysosomal CTSD activity not only enhanced
SNCA clearance in human and murine neurons as well as tissue, but also
restored endo-lysosome and autophagy function. Our findings indicate
that CTSD is critical for SNCA clearance and function. Thus, enzyme
replacement strategies utilizing CTSD may also be of therapeutic
interest for the treatment of PD and other synucleinopathies aiming to
decrease the SNCA burden.Abbreviations: aa: amino acid;
SNCA/α-synuclein: synuclein alpha; APP: amyloid beta precursor protein;
BBB: blood brain barrier; BF: basal forebrain; CBB: Coomassie Brilliant
Blue; CLN: neuronal ceroid lipofuscinosis; CNL10: neuronal ceroid
lipofuscinosis type 10; Corr.: corrected; CTSD: cathepsin D; CTSB:
cathepsin B; DA: dopaminergic; DA-iPSn: induced pluripotent stem
cell-derived dopaminergic neurons; dox: doxycycline; ERT: enzyme
replacement therapy; Fx: fornix, GBA/β-glucocerebrosidase:
glucosylceramidase beta; h: hour; HC: hippocampus; HT: hypothalamus;
i.c.: intracranially; IF: immunofluorescence; iPSC: induced pluripotent
stem cell; KO: knockout; LAMP1: lysosomal associated membrane protein 1;
LSDs: lysosomal storage disorders; MAPT: microtubule associated protein
tau; M6P: mannose-6-phosphate; M6PR: mannose-6-phosphate receptor; MB:
midbrain; mCTSD: mature form of CTSD; neurofil.: neurofilament; PD:
Parkinson disease; proCTSD: proform of CTSD; PRNP: prion protein; RFU:
relative fluorescence units; rHsCTSD: recombinant human proCTSD; SAPC:
Saposin C; SIM: structured illumination microscopy; T-insol:
Triton-insoluble; T-sol: Triton-soluble; TEM: transmission electron
microscopy, TH: tyrosine hydroxylase; Thal: thalamus.},
author = {Huarcaya, Alice Prieto and Drobny, Susy and Marques, Andre R. A. and Di Spiezio, Alessandro and Dobert, Jan and Balta, Denise and Werner, Christian and Rizo Garza, Tania and Gallwitz, Lisa and Bub, Simon and Stojkovska, Iva and Belur, Nandkishore R. and Fogh, Jens and Mazzulli, Joseph R. and Xiang, Wei and Fulzele, Amitkumar and Dejung, Mario and Sauer, Markus and Winner, Beate and Rose-John, Stefan and Arnold, Philipp and Saftig, Paul and Zunke, Friederike},
doi = {10.1080/15548627.2022.2045534},
faupublication = {yes},
journal = {Autophagy},
keywords = {alpha-synuclein; cathepsin D; lysosomal degradation; lysosomal storage disorders; parkinson disease; synucleinopathies},
pages = {1127-1151},
peerreviewed = {Yes},
title = {{Recombinant} pro-{CTSD} (cathepsin {D}) enhances {SNCA}/α-{Synuclein} degradation in α-{Synucleinopathy} models.},
volume = {18},
year = {2022}
}
@article{faucris.109448504,
abstract = {Troyer syndrome is an autosomal recessive form of complex hereditary spastic paraplegia. To date, the disorder has only been described in the Amish and in kindred from Oman. In Amish, all affected individuals have a homozygous one nucleotide deletion; c.1110delA. In the Omani kindred, all affected have a homozygous two nucleotides deletion; c.364{\_}365delTA (p.Met122ValfsTer2). Here we report the results of homozygosity mapping and whole exome sequencing in two siblings of a consanguineous Turkish family with mild intellectual disability, spastic paraplegia, and muscular dystrophy. We identified the same deletion that has been identified in the Omani kindred, but haplotype analysis suggests a recurrent event, and not a founder mutation. We summarize current knowledge of Troyer syndrome, and propose wider use of whole exome sequencing in routine diagnostics. This applies in particular to nonspecific phenotypes with high heterogeneity, such as spastic paraplegia, intellectual disability, and muscular dystrophy, since in such cases the assignment of a definite diagnosis is frequently delayed.},
author = {Tawamie, Hasan and Wohlleber, Eva and Uebe, Steffen and Schmael, Christine and Noethen, Markus M. and Abou Jamra, Rami},
doi = {10.1016/j.mcp.2015.05.006},
faupublication = {yes},
journal = {Molecular and Cellular Probes},
note = {EVALuna2:9263},
pages = {315-8},
peerreviewed = {Yes},
title = {{Recurrent} null mutation in {SPG20} leads to {Troyer} syndrome},
volume = {29},
year = {2015}
}
@article{faucris.280954448,
abstract = {Several mutations that cause Parkinson’s disease (PD) have been identified over the past decade. These account for 15–25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from the induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, show changes that are central and convergent to PD and suggest a strong involvement of the tetra-partite synapse in PD pathophysiology.},
author = {Stern, Shani and Lau, Shong and Manole, Andreea and Rosh, Idan and Percia, Menachem Mendel and Ben Ezer, Ran and Shokhirev, Maxim N. and Qiu, Fan and Schafer, Simon and Mansour, Abed Alfatah and Mangan, Kile P. and Stern, Tchelet and Ofer, Polina and Stern, Yam and Mendes, Ana Paula Diniz and Djamus, Jose and Moore, Lynne Randolph and Nayak, Ritu and Laufer, Sapir Havusha and Aicher, Aidan and Rhee, Amanda and Wong, Thomas L. and Thao Nguyen, and Linker, Sara B. and Winner, Beate and Freitas, Beatriz C. and Jones, Eugenia and Sagi, Irit and Bardy, Cedric and Brice, Alexis and Winkler, Jürgen and Marchetto, Maria C. and Gage, Fred H.},
doi = {10.1038/s41531-022-00366-z},
faupublication = {yes},
journal = {npj Parkinson’s Disease},
note = {CRIS-Team Scopus Importer:2022-08-26},
pages = {103},
peerreviewed = {Yes},
title = {{Reduced} synaptic activity and dysregulated extracellular matrix pathways in midbrain neurons from {Parkinson}’s disease patients},
volume = {8},
year = {2022}
}
@article{faucris.119746704,
abstract = {Purpose. Pseudoexfoliation (PEX) syndrome/glaucoma is a complex, late-onset disorder of the elastic fiber system. Strong genetic risk is conferred by the lysyl oxidase-like 1 (LOXL1) gene, but additional comodulating factors are necessary for the manifestation of the disease. The aim of this study was to analyze the effect of various PEX-associated pathogenic factors on the genotype-correlated expression of LOXL1 and elastin-related genes. Methods. Cultured human Tenon's capsule fibroblasts with high- and low-risk LOXL1 haplotypes were exposed to transforming growth factor (TGF)-?1, interleukin (IL)-6, homocysteine, oxidative stress, hypoxia, or ultraviolet (UV) radiation. Changes in the expression of LOXL1 and elastic constituents of PEX material and TGF-?1 were assessed by quantitative real-time PCR, Western blotting, immunohistochemistry, and electron microscopy. Results. Treatment of fibroblasts with TGF-?1, oxidative stress, UV light, and hypoxia induced a significant increase in expression levels of LOXL1 and elastic proteins, whereas the effect of IL-6 was limited to induction of elastic constituents. Immunohistochemistry and electron microscopy confirmed an upregulation of LOXL1 and elastic fiber proteins and their assembly into extracellular microfibrillar networks with focal aggregation of microfibrils into PEX-like fibrils on stimulation with TGF-?1 and oxidative stress. Basal and stimulated expression of LOXL1 mRNA and protein was slightly decreased in cells carrying the high-risk compared with the low-risk haplotype of LOXL1, but the differences between groups were statistically not significant. Conclusions. The findings support the notion that both genetic and nongenetic fibrogenic factors, particularly TGF-?1 and oxidative stress, may cooperate in the stable accumulation of PEX aggregates.},
author = {Zenkel, Matthias and Krysta, Anita and Pasutto, Francesca and Jünemann, Anselm and Kruse, Friedrich and Schlötzer-Schrehardt, Ursula},
doi = {10.1167/iovs.11-8361},
faupublication = {yes},
journal = {Investigative Ophthalmology & Visual Science},
note = {EVALuna2:9087},
pages = {8488-95},
peerreviewed = {Yes},
title = {{Regulation} of {Lysyl} {Oxidase}-like 1 ({LOXL1}) and {Elastin}-{Related} {Genes} by {Pathogenic} {Factors} {Associated} with {Pseudoexfoliation} {Syndrome}},
volume = {52},
year = {2011}
}
@article{faucris.245471927,
abstract = {Objectives: Eosinophils possess pro-inflammatory functions in asthma. However, our recent studies have suggested that innate lymphoid cells type 2 (ILC2s) and eosinophils have proresolving properties in rheumatoid arthritis (RA). Nothing is known yet about the mechanisms determining the double-edged role of eosinophils. Therefore, we investigated whether asthma, a paradigm eosinophilic disease, can elicit resolution of chronic arthritis. Methods: Ovalbumin-triggered eosinophilic asthma was combined with K/BxN serum-induced arthritis, where lung and synovial eosinophil subsets were compared by single-cell RNA sequencing (scRNA-seq). To investigate the involvement of the ILC2-interleukin-5 (IL-5) axis, hydrodynamic injection (HDI) of IL-25 and IL-33 plasmids, IL-5 reporter mice and anti-IL-5 antibody treatment were used. In patients with RA, the presence of distinct eosinophil subsets was examined in peripheral blood and synovial tissue. Disease activity of patients with RA with concomitant asthma was monitored before and after mepolizumab (anti-IL-5 antibody) therapy. Results: The induction of eosinophilic asthma caused resolution of murine arthritis and joint tissue protection. ScRNA-seq revealed a specific subset of regulatory eosinophils (rEos) in the joints, distinct from inflammatory eosinophils in the lungs. Mechanistically, synovial rEos expanded on systemic upregulation of IL-5 released by lung ILC2s. Eosinophil depletion abolished the beneficial effect of asthma on arthritis. rEos were consistently present in the synovium of patients with RA in remission, but not in active stage. Remarkably, in patients with RA with concomitant asthma, mepolizumab treatment induced relapse of arthritis. Conclusion: These findings point to a hitherto undiscovered proresolving signature in an eosinophil subset that stimulates arthritis resolution.},
author = {Andreev, Darja and Liu, Mengdan and Kachler, Katerina and Llerins Perez, Mireia and Kirchner, Philipp and Kölle, Julia and Gießl, Andreas and Rauber, Simon and Song, Rui and Aust, Oliver and Grüneboom, Anika and Kleyer, Arnd and Cañete, Juan D. and Ekici, Arif Bülent and Ramming, Andreas and Finotto, Susetta and Schett, Georg and Bozec, Aline},
doi = {10.1136/annrheumdis-2020-218902},
faupublication = {yes},
journal = {Annals of the Rheumatic Diseases},
keywords = {arthritis; autoimmune diseases; cytokines; immune system diseases; inflammation; rheumatoid},
note = {CRIS-Team Scopus Importer:2020-11-20},
peerreviewed = {Yes},
title = {{Regulatory} eosinophils induce the resolution of experimental arthritis and appear in remission state of human rheumatoid arthritis},
year = {2020}
}
@article{faucris.108188344,
abstract = {For decades, ill-defined autosomal dominant renal diseases have been reported, which originate from tubular cells and lead to tubular atrophy and interstitial fibrosis. These diseases are clinically indistinguishable, but caused by mutations in at least four different genes: UMOD, HNF1B, REN, and, as recently described, MUC1. Affected family members show renal fibrosis in the biopsy and gradually declining renal function, with renal failure usually occurring between the third and sixth decade of life. Here we describe 10 families and define eligibility criteria to consider this type of inherited disease, as well as propose a practicable approach for diagnosis. In contrast to what the frequently used term 'Medullary Cystic Kidney Disease' implies, development of (medullary) cysts is neither an early nor a typical feature, as determined by MRI. In addition to Sanger and gene panel sequencing of the four genes, we established SNaPshot minisequencing for the predescribed cytosine duplication within a distinct repeat region of MUC1 causing a frameshift. A mutation was found in 7 of 9 families (3 in UMOD and 4 in MUC1), with one indeterminate (UMOD p.T62P). On the basis of clinical and pathological characteristics we propose the term 'Autosomal Dominant Tubulointerstitial Kidney Disease' as an improved terminology. This should enhance recognition and correct diagnosis of affected individuals, facilitate genetic counseling, and stimulate research into the underlying pathophysiology.},
author = {Ekici, Arif Bülent and Hackenbeck, Thomas and Moriniere, Vincent and Panness, Andrea and Büttner, Maike and Uebe, Steffen and Janka, Rolf Matthias and Wiesener, Antje and Hermann, Ingo and Grupp, Sina and Hornberger, Martin and Huber, Tobias B. and Isbel, Nikky and Mangos, George and Mcginn, Stella and Soreth-Rieke, Daniela and Beck, Bodo B. and Uder, Michael and Amann, Kerstin Ute and Antignac, Corinne and Reis, André and Eckardt, Kai-Uwe and Wiesener, Michael S.},
doi = {10.1038/ki.2014.72},
faupublication = {yes},
journal = {Kidney International},
note = {EVALuna2:3695},
pages = {589-99},
peerreviewed = {Yes},
title = {{Renal} fibrosis is the common feature of autosomal dominant tubulointerstitial kidney diseases caused by mutations in mucin 1 or uromodulin},
volume = {86},
year = {2014}
}
@article{faucris.111192004,
author = {Budu-Aggrey, Ashley and Bowes, John and Loehr, Sabine and Uebe, Steffen and Zervou, Maria I. and Helliwell, Philip and Ryan, Anthony W. and Kane, David and Korendowych, Eleanor and Giardina, Emiliano and Packham, Jonathan and Mcmanus, Ross and Fitzgerald, Oliver and Mchugh, Neil and Behrens, Frank and Burkhardt, Harald and Huffmeier, Ulrike and Ho, Pauline and Martin, Javier and Castaneda, Santos and Goulielmos, George and Reis, André and Barton, Anne},
doi = {10.1136/annrheumdis-2016-209290},
faupublication = {yes},
journal = {Annals of the Rheumatic Diseases},
note = {EVALuna2:9332},
pages = {1417-8},
peerreviewed = {Yes},
title = {{Replication} of a distinct psoriatic arthritis risk variant at the {IL23R} locus},
volume = {75},
year = {2016}
}
@article{faucris.122328844,
author = {Bergauer, Annika and Sopel, Nina and Kro, Bettina and Vuorinen, Tytti and Xepapadaki, Paraskevi and Weiss, Scott T. and Blau, Ashley and Sharma, Himanshu and Kraus, Cornelia and Springel, Rebekka and Rauh, Manfred and Mittler, Susanne and Graser, Anna and Zimmermann, Theodor and Melichar, Volker O. and Kiefer, Alexander and Kowalski, Marek L. and Sobanska, Anna and Jartti, Tuomas and Lukkarinen, Heikki and Papadopoulos, Nikolaos G. and Finotto, Susetta},
doi = {10.1183/13993003.00265-2017},
faupublication = {yes},
journal = {European Respiratory Journal},
note = {EVALuna2:25986},
peerreviewed = {Yes},
title = {{Rhinovirus} species/genotypes and interferon-λ: subtypes, receptor and polymorphisms - missing pieces of the puzzle of childhood asthma?},
volume = {49},
year = {2017}
}
@article{faucris.204853569,
abstract = {Over the last two decades genetic testing for mutations in BRCA1 and BRCA2 has become standard of care for women and men who are at familial risk for breast or ovarian cancer. Currently, genetic testing more often also includes so-called panel genes, which are assumed to be moderate-risk genes for breast cancer. Recently, new large-scale studies provided more information about the risk estimation of those genes. The utilization of information on panel genes with regard to their association with the individual breast cancer risk might become part of future clinical practice. Furthermore, large efforts have been made to understand the influence of common genetic variants with a low impact on breast cancer risk. For this purpose, almost 450 000 individuals have been genotyped for almost 500 000 genetic variants in the OncoArray project. Based on first results it can be assumed that - together with previously identified common variants - more than 170 breast cancer risk single nucleotide polymorphisms can explain up to 18% of familial breast cancer risk. The knowledge about genetic and non-genetic risk factors and its implementation in clinical practice could especially be of use for individualized prevention. This includes an individualized risk prediction as well as the individualized selection of screening methods regarding imaging and possible lifestyle interventions. The aim of this review is to summarize the most recent developments in this area and to provide an overview on breast cancer risk genes, risk prediction models and their utilization for the individual patient.},
author = {Wunderle, Marius and Olmes, Gregor and Nabieva, Naiba and Häberle, Lothar and Jud, Sebastian and Hein, Alexander and Rauh, Claudia and Hack, Carolin and Erber, Ramona and Ekici, Arif Bülent and Hoyer, Juliane and Vasileiou, Georgia and Kraus, Cornelia and Reis, André and Hartmann, Arndt and Schulz-Wendtland, Rüdiger and Lux, Michael P. and Beckmann, Matthias and Fasching, Peter},
doi = {10.1055/a-0603-4350},
faupublication = {yes},
journal = {Geburtshilfe und Frauenheilkunde},
note = {EVALuna2:34612},
pages = {481-492},
peerreviewed = {Yes},
title = {{Risk}, {Prediction} and {Prevention} of {Hereditary} {Breast} {Cancer} - {Large}-{Scale} {Genomic} {Studies} in {Times} of {Big} and {Smart} {Data}},
volume = {78},
year = {2018}
}
@inproceedings{faucris.207813880,
author = {Pasutto, Francesca and Zenkel, Matthias and Berner, Daniel and Uebe, Steffen and Ekici, Arif Bülent and Kruse, Friedrich and Reis, André and Schlötzer-Schrehardt, Ursula},
faupublication = {yes},
note = {EVALuna2:34745},
peerreviewed = {Yes},
title = {{RNA}-seq and pathway analysis of ocular tissues in {PEX} patients and healthy subjects},
volume = {59},
year = {2018}
}
@article{faucris.264301487,
abstract = {Abstract: In malignant hypertension, far more severe kidney injury occurs than in the “benign” form of the disease. The role of high blood pressure and the renin–angiotensin–aldosterone system is well recognized, but the pathogenesis of the renal injury of malignant hypertension (MH) remains incompletely understood. Using the rat model of two-kidney, one-clip renovascular hypertension in which some but not all animals develop MH, we performed a transcriptomic analysis of gene expression by RNA sequencing to identify transcriptional changes in the kidney cortex specific for MH. Differential gene expression was assessed in three groups: MH, non-malignant hypertension (NMH), and normotensive, sham-operated controls. To distinguish MH from NMH, we considered two factors: weight loss and typical renovascular lesions. Mean blood pressure measured intraarterially was elevated in MH (220 ± 6.5 mmHg) as well as in NMH (192 ± 6.4 mmHg), compared to controls (119 ± 1.7 mmHg, p < 0.05). Eight hundred eighty-six genes were exclusively regulated in MH only. Principal component analysis revealed a separated clustering of the three groups. The data pointed to an upregulation of many inflammatory mechanisms in MH including pathways which previously attracted relatively little attention in the setting of hypertensive kidney injury: Transcripts from all three complement activation pathways were upregulated in MH compared to NMH but not in NMH compared with controls; immunohistochemistry confirmed complement deposition in MH exclusively. The expression of chemokines attracting neutrophil granulocytes (CXCL6) and infiltration of myeloperoxidase-positive cells were increased only in MH rats. The data suggest that these pathways, especially complement deposition, may contribute to kidney injury under MH. Key messages: The most severe hypertension-induced kidney injury occurs in malignant hypertension.In a rat model of malignant hypertension, we assessed transcriptional responses in the kidney exposed to high blood pressure. A broad stimulation of inflammatory mechanisms was observed, but a few specific pathways were activated only in the malignant form of the disease, notably activation of the complement cascades.Complement inhibitors may alleviate the thrombotic microangiopathy of malignant hypertension even in the absence of primary complement abnormalities.},
author = {Menendez-Castro, Carlos and Cordasic, Nada and Fahlbusch, Fabian and Ekici, Arif Bülent and Kirchner, Philipp and Daniel, Christoph and Amann, Kerstin Ute and Velkeen, Roland and Wölfle, Joachim and Schiffer, Mario and Hartner, Andrea and Hilgers, Karl Friedrich},
doi = {10.1007/s00109-021-02133-8},
faupublication = {yes},
journal = {Journal of Molecular Medicine},
keywords = {Complement activation; Inflammation; Kidney injury; Malignant hypertension; RNA-Seq; Two-kidney one-clip renovascular hypertension (2K1C)},
note = {CRIS-Team Scopus Importer:2021-09-24},
peerreviewed = {Yes},
title = {{RNA} sequencing reveals induction of specific renal inflammatory pathways in a rat model of malignant hypertension},
year = {2021}
}
@article{faucris.236252283,
abstract = {Under normal conditions, the cornea, being the transparent "windscreen" of the eye, is free of both blood and lymphatic vessels. However, various diseases of the eye, like infections, can interfere with the balance between promoting and inhibiting factors, which leads to ingrowth of blood and lymphatic vessels. The newly formed lymphatic vessels increase the risk of graft rejection after subsequent corneal transplantation. Corneal transplantation is one of the most commonly performed transplantations worldwide, with more than 40,000 surgeries per year in Europe. To date, various anti-hem- and anti-lymphangiogenic treatment strategies have been developed specifically for the corneal vascular endothelial growth factor (VEGF) pathway. Currently, however, no treatment strategies are clinically available to specifically modulate lymphangiogenesis. In this review, we will give an overview about endogenous regulators of hem- and lymphangiogenesis and discuss potential new strategies for targeting pathological lymphangiogenesis. Furthermore, we will review recently identified modulators and demonstrate that the cornea is a suitable model for the identification of novel endogenous modulators of lymphangiogenesis. The identification of novel modulators of lymphangiogenesis and a better understanding of the signaling pathways involved will contribute to the development of new therapeutic targets for the treatment of pathological lymphangiogenesis. This, in turn, will improve graft rejection, not only for the cornea.},
author = {Clahsen, Thomas and Büttner, Christian and Hatami, Niloofar and Reis, André and Cursiefen, Claus},
doi = {10.3390/jcm9020479},
faupublication = {yes},
journal = {Journal of Clinical Medicine},
note = {CRIS-Team WoS Importer:2020-03-24},
peerreviewed = {Yes},
title = {{Role} of {Endogenous} {Regulators} of {Hem}- {And} {Lymphangiogenesis} in {Corneal} {Transplantation}},
volume = {9},
year = {2020}
}
@article{faucris.252783366,
abstract = {α-Synuclein has been reported to be important in modulating brain plasticity and to be a key protein in neurodegenerative diseases, including Lewy body dementia (LBD). We investigated how α-synuclein levels modulate adult neurogenesis and the development of dendritic arborization and spines in the dentate gyrus, in which new neurons are constantly added. In the human hippocampus, levels of endogenous α-synuclein were increased in LBD, and the numbers of SOX2-positive cells were decreased. We investigated whether newly generated neurons were modulated by endogenous α-synuclein, and we found increased adult neurogenesis in α/β-synuclein knock-out mice. In contrast, overexpression of human wild-type α-synuclein (WTS) decreased the survival and dendritic development of newborn neurons. Endogenous α-synuclein expression levels increased the negative impact of WTS on dendrite development, suggesting a toxic effect of increasing amounts of α-synuclein. To attempt a rescue of the dendritic phenotype, we administered rolipram to activate the cAMP response element-binding protein pathway, which led to a partial rescue of neurite development. The current work provides novel insights into the role of α-synuclein in adult hippocampal neurogenesis.},
author = {Winner, Beate and Regensburger, Martin and Prots, Iryna and Winkler, Jürgen and et al.},
author_hint = {Winner, Regensburger, Schreglmann, Boyer, Prots, Rockenstein, Mante, Zhao, Winkler, Masliah, Gage},
doi = {10.1523/JNEUROSCI.2723-12.2012},
faupublication = {no},
journal = {Journal of Neuroscience},
pages = {16906-16},
peerreviewed = {Yes},
support_note = {Author relations incomplete. You may find additional data in field 'author{\_}hint'},
title = {{Role} of α-synuclein in adult neurogenesis and neuronal maturation in the dentate gyrus.},
volume = {32},
year = {2012}
}
@article{faucris.209891736,
abstract = {Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3' gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97⁻1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03⁻1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10-28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.
},
author = {Kelemen, Linda E. and Earp, Madalene and Fridley, Brooke L. and Chenevix-Trench, Georgia and Fasching, Peter and Beckmann, Matthias and Ekici, Arif Bülent and Hein, Alexander and Lambrechts, Diether and Lambrechts, Sandrina and Van Nieuwenhuysen, Els and Vergote, Ignace and Rossing, Mary Anne and Doherty, Jennifer A. and Chang-Claude, Jenny and Behrens, Sabine and Moysich, Kirsten B. and Cannioto, Rikki and Lele, Shashikant and Odunsi, Kunle and Goodman, Marc T. and Shvetsov, Yurii B. and Thompson, Pamela J. and Wilkens, Lynne R. and Doerk, Thilo and Antonenkova, Natalia and Bogdanova, Natalia and Hillemanns, Peter and Runnebaum, Ingo B. and Du Bois, Andreas and Harter, Philipp and Heitz, Florian and Schwaab, Ira and Butzow, Ralf and Pelttari, Liisa M. and Nevanlinna, Heli and Modugno, Francesmary and Edwards, Robert P. and Kelley, Joseph L. and Ness, Roberta B. and Karlan, Beth Y. and Lester, Jenny and Orsulic, Sandra and Walsh, Christine and Kjaer, Susanne K. and Jensen, Allan and Cunningham, Julie M. and Vierkant, Robert A. and Giles, Graham G. and Bruinsma, Fiona and Southey, Melissa C. and Hildebrandt, Michelle A. T. and Liang, Dong and Lu, Karen and Wu, Xifeng and Sellers, Thomas A. and Levine, Douglas A. and Schildkraut, Joellen M. and Iversen, Edwin S. and Terry, Kathryn L. and Cramer, Daniel W. and Tworoger, Shelley S. and Poole, Elizabeth M. and Bandera, Elisa V. and Olson, Sara H. and Orlow, Irene and Thomsen, Liv Cecilie Vestrheim and Bjorge, Line and Krakstad, Camilla and Tangen, Ingvild L. and Kiemeney, Lambertus A. and Aben, Katja K. H. and Massuger, Leon F. A. G. and Van Altena, Anne M. and Pejovic, Tanja and Bean, Yukie and Kellar, Melissa and Cook, Linda S. and Le, Nhu D. and Brooks-Wilson, Angela and Gronwald, Jacek and Cybulski, Cezary and Jakubowska, Anna and Lubinski, Jan and Wentzensen, Nicolas and Brinton, Louise A. and Lissowska, Jolanta and Hogdall, Estrid and Engelholm, Svend Aage and Hogdall, Claus and Lundvall, Lene and Nedergaard, Lotte and Pharoah, Paul D. P. and Dicks, Ed and Song, Honglin and Tyrer, Jonathan P. and Mcneish, Iain and Siddiqui, Nadeem and Carty, Karen and Glasspool, Rosalind and Paul, James and Campbell, Ian G. and Eccles, Diana and Whittemore, Alice S. and Mcguire, Valerie and Rothstein, Joseph H. and Sieh, Weiva and Narod, Steven A. and Phelan, Catherine M. and Mclaughlin, John R. and Risch, Harvey A. and Anton-Culver, Hoda and Ziogas, Argyrios and Menon, Usha and Gayther, Simon A. and Gentry-Maharaj, Aleksandra and Ramus, Susan J. and Wu, Anna H. and Pearce, Celeste Leigh and Lee, Alice W. and Pike, Malcolm C. and Kupryjanczyk, Jolanta and Podgorska, Agnieszka and Plisiecka-Halasa, Joanna and Sawicki, Wlodzimierz and Goode, Ellen L. and Berchuck, Andrew},
doi = {10.3390/ijms19092473},
faupublication = {yes},
journal = {International Journal of Molecular Sciences},
note = {EVALuna2:35118},
peerreviewed = {Yes},
title = {rs495139 in the {TYMS}-{ENOSF1} {Region} and {Risk} of {Ovarian} {Carcinoma} of {Mucinous} {Histology}},
volume = {19},
year = {2018}
}
@inproceedings{faucris.248110411,
address = {LONDON},
author = {Fliedner, Anna and Kirchner, P. and Agre, K. E. and De Graaf-Van De Laar, I. and Clarke, M. Dutra and Davis-Keppen, L. and Ekici, Arif Bülent and Gregor, Anne and Lippa, N. and Mcwalter, K. and Mirzaa, G. and Noh, G. and Ohden, L. and Scott, D. A. and Lalani, S. and Straussberg, R. and Cohen, R. and Wiesener, A. and Zweier, Christiane},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {31-32},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{SCAF4} loss of function in humans and {Drosophila} implicates {mRNA} transcriptional termination in neuro-developmental disorders},
year = {2020}
}
@article{faucris.308934982,
abstract = {Conventional 2D cultures are commonly used in cancer research though they come with limitations such as the lack of microenvironment or reduced cell heterogeneity. In this study, we investigated in what respect a scaffold-based (Matrigel™) 3D culture technique can ameliorate the limitations of 2D cultures. NGS-based bulk and single-cell sequencing of matched pairs of 2D and 3D models showed an altered transcription of key immune regulatory genes in around 36% of 3D models, indicating the reoccurrence of an immune suppressive phenotype. Changes included the presentation of different HLA surface molecules as well as cellular stressors. We also investigated the 3D tumor organoids in a co-culture setting with tumor-infiltrating lymphocytes (TILs). Of note, lymphocyte-mediated cell killing appeared less effective in clearing 3D models than their 2D counterparts. IFN-γ release, as well as live cell staining and proliferation analysis, pointed toward an elevated resistance of 3D models. In conclusion, we found that the scaffold-based (Matrigel™) 3D culture technique affects the transcriptional profile in a subset of GBM models. Thus, these models allow for depicting clinically relevant aspects of tumor-immune interaction, with the potential to explore immunotherapeutic approaches in an easily accessible in vitro system.},
author = {Braun, Frank K. and Rothhammer-Hampl, Tanja and Lorenz, Julia and Pohl, Sandra and Menevse, Ayse Nur and Vollmann-Zwerenz, Arabel and Bumes, Elisabeth and Büttner, Maren and Zoubaa, Saida and Proescholdt, Martin and Schmidt, Nils O. and Hau, Peter and Beckhove, Philipp and Winner, Beate and Riemenschneider, Markus J.},
doi = {10.3390/cells12141856},
faupublication = {yes},
journal = {Cells},
keywords = {brain cancer; GBM; next-generation sequencing; single-cell RNA sequencing; tumor organoids},
note = {CRIS-Team Scopus Importer:2023-08-11},
peerreviewed = {Yes},
title = {{Scaffold}-{Based} ({Matrigel}™) {3D} {Culture} {Technique} of {Glioblastoma} {Recovers} a {Patient}-like {Immunosuppressive} {Phenotype}},
volume = {12},
year = {2023}
}
@article{faucris.262669186,
abstract = {Transcription factor 4 (TCF4) is a crucial regulator of neurodevelopment and has been linked to the pathogenesis of autism, intellectual disability and schizophrenia. As a class I bHLH transcription factor (TF), it is assumed that TCF4 exerts its neurodevelopmental functions through dimerization with proneural class II bHLH TFs. Here, we aim to identify TF partners of TCF4 in the control of interhemispheric connectivity formation. Using a new bioinformatic strategy integrating TF expression levels and regulon activities from single cell RNA-sequencing data, we find evidence that TCF4 interacts with non-bHLH TFs and modulates their transcriptional activity in Satb2+ intercortical projection neurons. Notably, this network comprises regulators linked to the pathogenesis of neurodevelopmental disorders, e.g. FOXG1, SOX11 and BRG1. In support of the functional interaction of TCF4 with non-bHLH TFs, we find that TCF4 and SOX11 biochemically interact and cooperatively control commissure formation in vivo, and regulate the transcription of genes implicated in this process. In addition to identifying new candidate interactors of TCF4 in neurodevelopment, this study illustrates how scRNA-Seq data can be leveraged to predict TF networks in neurodevelopmental processes.},
author = {Wittmann, Marie-Theres and Katada, Sayako and Sock, Elisabeth and Kirchner, Philipp and Ekici, Arif Bülent and Wegner, Michael and Nakashima, Kinichi and Lie, Dieter Chichung and Reis, André},
doi = {10.1242/DEV.196022},
faupublication = {yes},
journal = {Development},
keywords = {Commissure development; Gene regulatory networks; Mouse; Protein-protein interaction; Single-cell RNA sequencing; SOX11; TCF4},
note = {CRIS-Team Scopus Importer:2021-08-13},
peerreviewed = {Yes},
title = {{scRNA} sequencing uncovers a {TCF4}-dependent transcription factor network regulating commissure development in mouse},
volume = {148},
year = {2021}
}
@article{faucris.208945865,
abstract = {Spermatogenesis is an efficient and complex system of continuous cell differentiation. Previous studies investigating the transcriptomes of different cell populations in the testis relied either on sorting cells, cell depletion, or juvenile animals where not all stages of spermatogenesis have been completed. We present single-cell RNA sequencing (scRNA-Seq) data of 2,500 cells from the testes of two 8-week-old C57Bl/6J mice. Our dataset includes all spermatogenic stages from preleptotene to condensing spermatids as well as individual spermatogonia, Sertoli and Leydig cells. The data capture the full continuity of the meiotic and postmeiotic stages of spermatogenesis, and is thus ideally suited for marker discovery, network inference and similar analyses for which temporal ordering of differentiation processes can be exploited. Furthermore, it can serve as a reference for future studies involving single-cell RNA-Seq in mice where spermatogenesis is perturbed.
},
author = {Lukassen, Sören and Bosch, Elisabeth and Ekici, Arif Bülent and Winterpacht, Andreas},
doi = {10.1038/sdata.2018.192},
faupublication = {yes},
journal = {Scientific Data},
note = {EVALuna2:34826},
peerreviewed = {Yes},
title = {{Single}-cell {RNA} sequencing of adult mouse testes},
volume = {5},
year = {2018}
}
@article{faucris.204402075,
abstract = {Recently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel sequencing methods due to the complexity of the VNTR. We established long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay. Our approach allows complete VNTR assembly, thereby enabling the detection of all variants residing within the VNTR and simultaneous determination of VNTR length. We present high resolution data on the VNTR architecture for a cohort of snapshot positive (n = 9) and negative (n = 7) ADTKD families. By SMRT sequencing we could confirm the diagnosis in all previously tested cases, reconstruct both VNTR alleles and determine the exact position of the causative variant in eight of nine families. This study demonstrates that precise positioning of the causative mutation(s) and identification of other coding and noncoding sequence variants in ADTKD-MUC1 is feasible. SMRT sequencing could provide a powerful tool to uncover potential factors encoded within the VNTR that associate with intra- and interfamilial phenotype variability of MUC1 related kidney disease.},
author = {Wenzel, Andrea and Altmueller, Janine and Ekici, Arif Bülent and Popp, Bernt and Stueber, Kurt and Thiele, Holger and Pannes, Alois and Staubach, Simon and Salido, Eduardo and Nuernberg, Peter and Reinhardt, Richard and Reis, André and Rump, Patrick and Hanisch, Franz-Georg and Wolf, Matthias T. F. and Wiesener, Michael and Huettel, Bruno and Beck, Bodo B.},
doi = {10.1038/s41598-018-22428-0},
faupublication = {yes},
journal = {Scientific Reports},
note = {EVALuna2:34138},
peerreviewed = {Yes},
title = {{Single} molecule real time sequencing in {ADTKD}-{MUC1} allows complete assembly of the {VNTR} and exact positioning of causative mutations},
volume = {8},
year = {2018}
}
@article{faucris.229208377,
abstract = {Ayme-Gripp syndrome (AYGRPS) is a recognizable condition caused by a restricted spectrum of dominantly acting missense mutations affecting the transcription factor MAF. Major clinical features of AYGRPS include congenital cataracts, sensorineural hearing loss, intellectual disability, and a distinctive flat facial appearance. Skeletal abnormalities have also been observed in affected individuals, even though these features have not been assessed systematically. Expanding the series with four additional patients, here we provide a more accurate delineation of the molecular aspects and clinical phenotype, particularly focusing on the skeletal features characterizing this disorder. Apart from previously reported malar flattening and joint limitations, we document that carpal/tarsal and long bone defects, and hip dysplasia occur in affected subjects more frequently than formerly appreciated.},
author = {Niceta, Marcello and Barbuti, Domenico and Gupta, Neerja and Ruggiero, Carlos and Tizzano, Eduardo F. and Graul-Neumann, Luitgard and Barresi, Sabina and Nishimura, Gen and Valenzuela, Irene and Lopez-Grondona, Fermina and Fernandez-Alvarez, Paula and Leoni, Chiara and Zweier, Christiane and Tzschach, Andreas and Stellacci, Emilia and Del Fattore, Andrea and Dallapiccola, Bruno and Zampino, Giuseppe and Tartaglia, Marco},
doi = {10.1111/cge.13651},
faupublication = {yes},
journal = {Clinical Genetics},
note = {CRIS-Team WoS Importer:2019-11-15},
peerreviewed = {Yes},
title = {{Skeletal} abnormalities are common features in {Ayme}-{Gripp} syndrome},
year = {2019}
}
@inproceedings{faucris.228302266,
address = {LONDON},
author = {Niceta, M. and Del Fattore, A. and Barbuti, D. and Rossi, M. and Stellacci, E. and Gupta, N. and Ruggiero, C. and Tizzano, E. and Graul-Neumann, L. and Leoni, C. and Zweier, Christiane and Fernandez Alvarez, P. and Tzschach, A. and Valenzuela, M. and Barresi, S. and Dallapiccola, B. and Zampino, G. and Tartaglia, M. and Nishimura, G.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2019-06-15/2019-06-18},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {1495-1496},
peerreviewed = {unknown},
publisher = {NATURE PUBLISHING GROUP},
title = {{Skeletal} defects and defective osteoclast and osteoblast function in {Ayme}-{Gripp} syndrome},
venue = {Gothenburg, SWEDEN},
year = {2019}
}
@article{faucris.238799556,
abstract = {Neuronal activity initiates transcriptional programs that shape long-term changes in plasticity. Although neuron subtypes differ in their plasticity response, most activity-dependent transcription factors (TFs) are broadly expressed across neuron subtypes and brain regions. Thus, how region- and neuronal subtype-specific plasticity are established on the transcriptional level remains poorly understood. We report that in young adult (i.e., 6-8 weeks old) mice, the developmental TF SOX11 is induced in neurons within 6 h either by electroconvulsive stimulation or by exploration of a novel environment. Strikingly, SOX11 induction was restricted to the dentate gyrus (DG) of the hippocampus. In the novel environment paradigm, SOX11 was observed in a subset of c-FOS expressing neurons (ca. 15%); whereas around 75% of SOX11+ DG granule neurons were c-FOS+, indicating that SOX11 was induced in an activity-dependent fashion in a subset of neurons. Environmental enrichment or virus-mediated overexpression of SOX11 enhanced the excitability of DG granule cells and downregulated the expression of different potassium channel subunits, whereas conditional Sox11/4 knock-out mice presented the opposite phenotype. We propose that Sox11 is regulated in an activity-dependent fashion, which is specific to the DG, and speculate that activity-dependent Sox11 expression may participate in the modulation of DG neuron plasticity.},
author = {von Wittgenstein, Julia and Zheng, Fang and Wittmann, Marie-Theres and Balta, Elli-Anna and Ferrazzi, Fulvia and Schäffner, Iris and Häberle, Benjamin and Valero Aracama, Maria Jesus and Koehl, Muriel and Miranda, Carlos J. and Kaspar, Brian K. and Ekici, Arif Bülent and Reis, André and Abrous, Djoher Nora and Alzheimer, Christian and Lie, Dieter Chichung},
doi = {10.1093/cercor/bhz338},
faupublication = {yes},
journal = {Cerebral Cortex},
keywords = {dentate gyrus; hippocampus; immediate early gene; plasticity; Sox11},
note = {CRIS-Team Scopus Importer:2020-05-29},
pages = {3731-3743},
peerreviewed = {Yes},
title = {{Sox11} is an {Activity}-{Regulated} {Gene} with {Dentate}-{Gyrus}-{Specific} {Expression} {Upon} {General} {Neural} {Activation}},
volume = {30},
year = {2020}
}
@article{faucris.119189664,
abstract = {We examined an extended, consanguineous family with seven individuals with severe intellectual disability and microcephaly. Further symptoms were hearing loss, vision impairment, gastrointestinal disturbances, and slow and asymmetric waves in the EEG. Linkage analysis followed by exome sequencing revealed a homozygous variant in SPATA5 (c.1822{\_}1824del; p.Asp608del), which segregates with the phenotype in the family. Molecular modelling suggested a deleterious effect of the identified alterations on the protein function. In an unrelated family, we identified compound heterozygous variants in SPATA5 (c.[2081G > A];[989{\_}991delCAA]; p.[Gly694Glu];[.Thr330del]) in a further individual with global developmental delay, infantile spasms, profound dystonia, and sensorineural hearing loss. Molecular modelling suggested an impairment of protein function in the presence of both variants.SPATA5 is a member of the ATPase associated with diverse activities (AAA) protein family and was very recently reported in one publication to be mutated in individuals with intellectual disability, epilepsy and hearing loss. Our results describe new, probably pathogenic variants in SPATA5 that were identified in individuals with a comparable phenotype. We thus independently confirm that bi-allelic pathogenic variants in SPATA5 cause a syndromic form of intellectual disability, and we delineate its clinical presentation.},
author = {Buchert, Rebecca and Nesbitt, Addie I. and Tawamie, Hasan and Krantz, Ian D. and Medne, Livija and Helbig, Ingo and Matalon, Dena R. and Reis, André and Santani, Avni and Sticht, Heinrich and Abou Jamra, Rami},
doi = {10.1186/s13023-016-0509-9},
faupublication = {yes},
journal = {Orphanet Journal of Rare Diseases},
note = {EVALuna2:9313},
pages = {130},
peerreviewed = {Yes},
title = {{SPATA5} mutations cause a distinct autosomal recessive phenotype of intellectual disability, hypotonia and hearing loss},
volume = {11},
year = {2016}
}
@inproceedings{faucris.228304787,
address = {LONDON},
author = {Zweier, M. and Begemann, A. and Mcwalter, K. and Cho, M. T. and Abela, L. and Banka, S. and Behring, B. and Berger, A. and Brown, C. W. and Carneiro, M. and Chen, J. and Cooper, G. M. and Finnila, C. R. and Sacoto, M. J. Guillen and Henderson, A. and Hüffmeier, Ulrike and Joset, P. and Kerr, B. and Lesca, G. and Leszinski, G. S. and Mcdermott, J. H. and Meltzer, M. R. and Monaghan, K. G. and Mostafavi, R. and Ounap, K. and Plecko, B. and Powis, Z. and Purcarin, G. and Reimand, T. and Riedhammer, K. M. and Schreiber, J. M. and Sirsi, D. and Wierenga, K. J. and Wojcik, M. H. and Papuc, S. M. and Steindl, K. and Sticht, Heinrich and Rauch, A.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
date = {2019-06-15/2019-06-18},
doi = {10.1038/s41431-018-0331-z},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2019-10-25},
pages = {1383-1384},
peerreviewed = {Yes},
publisher = {NATURE PUBLISHING GROUP},
title = {{Spatially} clustering de novo variants in {CYFIP2}, encoding the cytoplasmic {FMRP} interacting protein 2, cause intellectual disability and seizures},
venue = {Gothenburg, SWEDEN},
year = {2019}
}
@article{faucris.216320684,
abstract = {CYFIP2, encoding the evolutionary highly conserved cytoplasmic FMRP interacting protein 2, has previously been proposed as a candidate gene for intellectual disability and autism because of its important role linking FMRP-dependent transcription regulation and actin polymerization via the WAVE regulatory complex (WRC). Recently, de novo variants affecting the amino acid p.Arg87 of CYFIP2 were reported in four individuals with epileptic encephalopathy. We here report 12 independent patients harboring a variety of de novo variants in CYFIP2 broadening the molecular and clinical spectrum of a novel CYFIP2-related neurodevelopmental disorder. Using trio whole-exome or -genome sequencing, we identified 12 independent patients carrying a total of eight distinct de novo variants in CYFIP2 with a shared phenotype of intellectual disability, seizures, and muscular hypotonia. We detected seven different missense variants, of which two occurred recurrently (p.(Arg87Cys) and p.(Ile664Met)), and a splice donor variant in the last intron for which we showed exon skipping in the transcript. The latter is expected to escape nonsense-mediated mRNA decay resulting in a truncated protein. Despite the large spacing in the primary structure, the variants spatially cluster in the tertiary structure and are all predicted to weaken the interaction with WAVE1 or NCKAP1 of the actin polymerization regulating WRC-complex. Preliminary genotype-phenotype correlation indicates a profound phenotype in p.Arg87 substitutions and a more variable phenotype in other alterations. This study evidenced a variety of de novo variants in CYFIP2 as a novel cause of mostly severe intellectual disability with seizures and muscular hypotonia.},
author = {Zweier, Markus and Begemann, Anais and Mcwalter, Kirsty and Cho, Megan T. and Abela, Lucia and Banka, Siddharth and Behring, Bettina and Berger, Andrea and Brown, Chester W. and Carneiro, Maryline and Chen, Jiani and Cooper, Gregory M. and Finnila, Candice R. and Sacoto, Maria J. Guillen and Henderson, Alex and Hüffmeier, Ulrike and Joset, Pascal and Kerr, Bronwyn and Lesca, Gaetan and Leszinski, Gloria S. and Mcdermott, John Henry and Meltzer, Meira R. and Monaghan, Kristin G. and Mostafavi, Roya and Ounap, Katrin and Plecko, Barbara and Powis, Zoe and Purcarin, Gabriela and Reimand, Tiia and Riedhammer, Korbinian M. and Schreiber, John M. and Sirsi, Deepa and Wierenga, Klaas J. and Wojcik, Monica H. and Papuc, Sorina M. and Steindl, Katharina and Sticht, Heinrich and Rauch, Anita},
doi = {10.1038/s41431-018-0331-z},
faupublication = {yes},
journal = {European journal of human genetics},
note = {CRIS-Team WoS Importer:2019-04-23},
pages = {747-759},
peerreviewed = {Yes},
title = {{Spatially} clustering de novo variants in {CYFIP2}, encoding the cytoplasmic {FMRP} interacting protein 2, cause intellectual disability and seizures},
volume = {27},
year = {2019}
}
@article{faucris.212593527,
abstract = {Differentiated neurons established via iPSCs from patients that suffer from familial Parkinson's disease (PD) have allowed insights into the mechanisms of neurodegeneration. In the larger cohort of patients with sporadic PD, iPSC based information on disease specific cellular phenotypes is rare. We asked whether differences may be present on genomic and epigenomic levels and performed a comprehensive transcriptomic and epigenomic analysis of fibroblasts, iPSCs and differentiated neuronal cells of sporadic PD-patients and controls. We found that on mRNA level, although fibroblasts and iPSCs are largely indistinguishable, differentiated neuronal cells of sporadic PD patients show significant alterations enriched in pathways known to be involved in disease aetiology, like the CREB-pathway and the pathway regulating PGC1a. Moreover, miRNAs and piRNAs/piRNA-like molecules are largely differentially regulated in cells and post-mortem tissue samples between control-and PD-patients. The most striking differences can be found in piRNAs/piRNA-like molecules, with SINE-and LINE-derived piRNAs highly downregulated in a disease specific manner. We conclude that neuronal cells derived from sporadic PD-patients help to elucidate novel disease mechanisms and provide relevant insight into the epigenetic landscape of sporadic Parkinson's disease as particularly regulated by small RNAs.},
author = {Schulze, Markus and Sommer, Annika and Plotz, Sonja and Farrell, Michaela and Winner, Beate and Grosch, Janina and Winkler, Jürgen and Riemenschneider, Markus J.},
doi = {10.1186/s40478-018-0561-x},
faupublication = {yes},
journal = {Acta Neuropathologica Communications},
note = {EVALuna2:35781},
peerreviewed = {Yes},
title = {{Sporadic} {Parkinson}'s disease derived neuronal cells show disease-specific {mRNA} and small {RNA} signatures with abundant deregulation of {piRNAs}},
volume = {6},
year = {2018}
}
@article{faucris.273201052,
abstract = {Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare metabolic disease mainly characterized by psychomotor disability, visual impairment, and variable eye malformations caused by bi-allelic pathogenic variants in SRD5A3. So far, only 23 distinct mutations were described. Exome sequencing in 32-year old monozygotic male twins revealed only the heterozygous splice variant c.562+3delG in SRD5A3, but no second variant. The twins presented with psychomotor deficit and a complex eye disease including retinal dystrophy, pallor of the papilla, nystagmus, and strabismus suggestive of SRD5A3-CDG. Only when applying exome-based copy number analysis, we identified as a second compound heterozygous variant a previously not reported tandem duplication of exons 2–4 in SRD5A3. Next to the typical skeletal anomalies of SRD5A3-CDG such as kyphosis and scoliosis, extension deficits of the proximal interphalangeal (PIP) joints IV were observed. Since similar contractures were described once in a patient with SRD5A3-CDG, we suggest that this rare symptom is possibly associated with SRD5A3-CDG. Our findings further expand the mutational and clinical spectrum of SRD5A3-CDG and emphasize the importance of an intragenic copy number analysis in patients with strong clinical suspicion of SRD5A3-CDG and only one detectable sequence variant.},
author = {Rieger, Melissa and Türk, Matthias and Kraus, Cornelia and Uebe, Steffen and Ekici, Arif Bülent and Krumbiegel, Mandy and Huchzermeyer, Cord and Wiesmann da Silva Reis, André and Thiel, Christian},
doi = {10.1016/j.ejmg.2022.104492},
faupublication = {yes},
journal = {European Journal of Medical Genetics},
keywords = {CDG; Exon duplication; SRD5A3},
note = {CRIS-Team Scopus Importer:2022-04-15},
peerreviewed = {Yes},
title = {{SRD5A3}-{CDG}: {Twins} with an intragenic tandem duplication},
volume = {65},
year = {2022}
}
@article{faucris.121820644,
abstract = {The human genome segment upstream of the FMR1 (fragile X mental retardation 1) gene (Xq27.3) contains several genetic signals, among them is a DNA methylation boundary that is located 65-70 CpGs upstream of the CGG repeat. In fragile X syndrome (FXS), the boundary is lost, and the promoter is inactivated by methylation spreading. Here we document boundary stability in spite of critical expansions of the CGG trinucleotide repeat in male or female premutation carriers and in high functioning males (HFMs). HFMs carry a full CGG repeat expansion but exhibit an unmethylated promoter and lack the FXS phenotype. The boundary is also stable in Turner (45, X) females. A CTCF-binding site is located slightly upstream of the methylation boundary and carries a unique G-to-A polymorphism (single nucleotide polymorphism), which occurs 3.6 times more frequently in genomes with CGG expansions. The increased frequency of this single nucleotide polymorphism might have functional significance. In CGG expansions, the CTCF region does not harbor additional mutations. In FXS individuals and often in cells transgenomic for EBV (Epstein Barr Virus) DNA or for the telomerase gene, the large number of normally methylated CpGs in the far-upstream region of the boundary is decreased about 4-fold. A methylation boundary is also present in the human genome segment upstream of the HTT (huntingtin) promoter (4p16.3) and is stable both in normal and Huntington disease chromosomes. Hence, the vicinity of an expanded repeat does not per se compromise methylation boundaries. Methylation boundaries exert an important function as promoter safeguards.},
author = {Naumann, Anja and Kraus, Cornelia and Hoogeveen, Andre and Ramirez, Christina M. and Doerfler, Walter},
doi = {10.1016/j.jmb.2014.04.025},
faupublication = {yes},
journal = {Journal of Molecular Biology},
note = {EVALuna2:8223},
pages = {2554-66},
peerreviewed = {Yes},
title = {{Stable} {DNA} methylation boundaries and expanded trinucleotide repeats: role of {DNA} insertions},
volume = {426},
year = {2014}
}
@article{faucris.120020824,
abstract = {Cohesinopathies are rare neurodevelopmental disorders arising from a dysfunction in the cohesin pathway, which enables chromosome segregation and regulates gene transcription. So far, eight genes from this pathway have been reported in human disease. STAG1 belongs to the STAG subunit of the core cohesin complex, along with five other subunits. This work aimed to identify the phenotype ascribed to STAG1 mutations.Among patients referred for intellectual disability (ID) in genetics departments worldwide, array-comparative genomic hybridisation (CGH), gene panel, whole-exome sequencing or whole-genome sequencing were performed following the local diagnostic standards.A mutation in STAG1 was identified in 17 individuals from 16 families, 9 males and 8 females aged 2-33 years. Four individuals harboured a small microdeletion encompassing STAG1; three individuals from two families had an intragenic STAG1 deletion. Six deletions were identified by array-CGH, one by whole-exome sequencing. Whole-exome sequencing found de novo heterozygous missense or frameshift STAG1 variants in eight patients, a panel of genes involved in ID identified a missense and a frameshift variant in two individuals. The 17 patients shared common facial features, with wide mouth and deep-set eyes. Four individuals had mild microcephaly, seven had epilepsy.We report an international series of 17 individuals from 16 families presenting with syndromic unspecific ID that could be attributed to a STAG1 deletion or point mutation. This first series reporting the phenotype ascribed to mutation in STAG1 highlights the importance of data sharing in the field of rare disorders.},
author = {Lehalle, Daphne and Mosca-Boidron, Anne-Laure and Begtrup, Amber and Boute-Benejean, Odile and Charles, Perrine and Cho, Megan T. and Clarkson, Amanda and Devinsky, Orrin and Duffourd, Yannis and Duplomb-Jego, Laurence and Gerard, Benedicte and Jacquette, Aurelia and Kuentz, Paul and Masurel-Paulet, Alice and Mcdougall, Carey and Moutton, Sebastien and Olivie, Hilde and Park, Soo-Mi and Rauch, Anita and Revencu, Nicole and Riviere, Jean-Baptiste and Rubin, Karol and Simonic, Ingrid and Shears, Deborah J. and Smol, Thomas and Tavares, Ana Lisa Taylor and Terhal, Paulien and Thevenon, Julien and Van Gassen, Koen and Vincent-Delorme, Catherine and Willemsen, Marjolein H. and Wilson, Golder N. and Zackai, Elaine and Zweier, Christiane and Callier, Patrick and Thauvin-Robinet, Christel and Faivre, Laurence},
doi = {10.1136/jmedgenet-2016-104468},
faupublication = {yes},
journal = {Journal of Medical Genetics},
note = {EVALuna2:9353},
pages = {479-488},
peerreviewed = {Yes},
title = {{STAG1} mutations cause a novel cohesinopathy characterised by unspecific syndromic intellectual disability},
volume = {54},
year = {2017}
}
@article{faucris.264062518,
abstract = {Intestinal homeostasis and the maintenance of the intestinal epithelial barrier are essential components of host defense during gastrointestinal Salmonella Typhimurium infection. Both require a strict regulation of cell death. However, the molecular pathways regulating epithelial cell death have not been completely understood. Here, we elucidated the contribution of central mechanisms of regulated cell death and upstream regulatory components during gastrointestinal infection. Mice lacking Caspase-8 in the intestinal epithelium are highly sensitive towards bacterial induced enteritis and intestinal inflammation, resulting in an enhanced lethality of these mice. This phenotype was associated with an increased STAT1 activation during Salmonella infection. Cell death, barrier breakdown and systemic infection were abrogated by an additional deletion of STAT1 in Casp8ΔIEC mice. In the absence of epithelial STAT1, loss of epithelial cells was abolished which was accompanied by a reduced Caspase-8 activation. Mechanistically, we demonstrate that epithelial STAT1 acts upstream of Caspase-8-dependent as well as -independent cell death and thus might play a major role at the crossroad of several central cell death pathways in the intestinal epithelium. In summary, we uncovered that transcriptional control of STAT1 is an essential host response mechanism that is required for the maintenance of intestinal barrier function and host survival.},
author = {Stolzer, Iris and Schickedanz, Laura and Chiriac, Mircea T. and López-Posadas, Rocío and Grassl, Guntram A. and Mattner, Jochen and Wirtz, Stefan and Neurath, Markus and Günther, Claudia and Winner, Beate},
doi = {10.1038/s41385-021-00450-2},
faupublication = {yes},
journal = {Mucosal Immunology},
note = {CRIS-Team Scopus Importer:2021-09-17},
pages = {130-142},
peerreviewed = {Yes},
title = {{STAT1} coordinates intestinal epithelial cell death during gastrointestinal infection upstream of {Caspase}-8},
volume = {15},
year = {2021}
}
@article{faucris.229374103,
abstract = {Objective: Cancer-associated fibroblasts (CAFs) influence the tumour microenvironment and tumour growth. However, the role of CAFs in colorectal cancer (CRC) development is incompletely understood. Design: We quantified phosphorylation of STAT3 (pSTAT3) expression in CAFs of human colon cancer tissue using a tissue microarray (TMA) of 375 patients, immunofluorescence staining and digital pathology. To investigate the functional role of CAFs in CRC, we took advantage of two murine models of colorectal neoplasia and advanced imaging technologies. In loss-of-function and gain-of-function experiments, using genetically modified mice with collagen type VI (COLVI)-specific signal transducer and activator of transcription 3 (STAT3) targeting, we evaluated STAT3 signalling in fibroblasts during colorectal tumour development. We performed a comparative gene expression profiling by whole genome RNA-sequencing of fibroblast subpopulations (COLVI+ vs COLVI-) on STAT3 activation (IL-6 vs IL-11). Results: The analysis of pSTAT3 expression in CAFs of human TMAs revealed a negative correlation of increased stromal pSTAT3 expression with the survival of colon cancer patients. In the loss-of-function and gain-of-function approach, we found a critical role of STAT3 activation in fibroblasts in driving colorectal tumourigenesis in vivo. With different imaging technologies, we detected an expansion of activated fibroblasts in colorectal neoplasias. Comparative gene expression profiling of fibroblast subpopulations on STAT3 activation revealed the regulation of transcriptional patterns associated with angiogenesis. Finally, the blockade of proangiogenic signalling significantly reduced colorectal tumour growth in mice with constitutive STAT3 activation in COLVI+ fibroblasts. Conclusion: Altogether our work demonstrates a critical role of STAT3 activation in CAFs in CRC development.},
author = {Heichler, Christina and Scheibe, Kristina and Schmied, Anabel and Geppert, Carol-Immanuel and Schmid, Benjamin and Wirtz, Stefan and Thoma, Oana Maria and Kramer, Viktoria and Waldner, Maximilian and Büttner, Christian and Farin, Henner and Pešić, Marina and Knieling, Ferdinand and Merkel, Susanne and Grüneboom, Anika and Gunzer, Matthias and Grützmann, Robert and Rose-John, Stefan and Koralov, Sergei and Kollias, George and Hartmann, Arndt and Greten, Florian and Neurath, Markus and Neufert, Clemens and Vieth, Michael},
doi = {10.1136/gutjnl-2019-319200},
faupublication = {yes},
journal = {Gut},
keywords = {colorectal cancer},
note = {CRIS-Team Scopus Importer:2019-11-19},
peerreviewed = {Yes},
title = {{STAT3} activation through {IL}-6/{IL}-11 in cancer-associated fibroblasts promotes colorectal tumour development and correlates with poor prognosis},
year = {2019}
}
@misc{faucris.280026133,
abstract = {Pathogenic variants in SPAST, the gene coding for spastin, are the single most common cause of hereditary spastic paraplegia, a progressive motor neuron disease. Spastin regulates key cellular functions, including microtubule-severing and endoplasmic reticulum-morphogenesis. However, it remains unclear how alterations in these cellular functions due to SPAST pathogenic variants result in motor neuron dysfunction. Since spastin influences both microtubule network and endoplasmic reticulum structure, we hypothesized that spastin is necessary for the regulation of Ca2+ homeostasis via store-operated calcium entry. Here, we show that the lack of spastin enlarges the endoplasmic reticulum and reduces store-operated calcium entry. In addition, elevated levels of different spastin variants induced clustering of STIM1 within the endoplasmic reticulum, altered the transport of STIM1 to the plasma membrane and reduced store-operated calcium entry, which could be rescued by exogenous expression of STIM1. Importantly, store-operated calcium entry was strongly reduced in induced pluripotent stem cell-derived neurons from hereditary spastic paraplegia patients with pathogenic variants in SPAST resulting in spastin haploinsufficiency. These neurons developed axonal swellings in response to lack of spastin. We were able to rescue both store-operated calcium entry and axonal swellings in SPAST patient neurons by restoring spastin levels, using CRISPR/Cas9 to correct the pathogenic variants in SPAST. These findings demonstrate that proper amounts of spastin are a key regulatory component for store-operated calcium entry mediated Ca2+ homeostasis and suggest store-operated calcium entry as a disease relevant mechanism of spastin-linked motor neuron disease.Rizo et al. use iPSC-derived neurons from patients to investigate how pathogenic variants in SPAST give rise to hereditary spastic paraplegia. They show that dysregulation of spastin, a microtubule- and ER-remodelling protein encoded by SPAST, alters the dynamics of the ER, resulting in aberrant Ca2+ regulation.},
author = {Winner, Beate and Rizo Garza, Tania and Gebhardt, Lisa and Riedlberger, Julia and Eberhardt, Esther and Fester, Lars and Alansary, Dalia and Winkler, Jürgen and Turan, Sören and Arnold, Philipp and Niemeyer, Barbara and Fischer, Michael},
doi = {10.1093/brain/awac122},
faupublication = {yes},
keywords = {spastin;STIM1;microtubules;endoplasmic reticulum;store-operated calcium entry},
peerreviewed = {automatic},
title = {{Store}-operated calcium entry is reduced in spastin-linked hereditary spastic paraplegia},
url = {https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awac122/6651093},
year = {2022}
}
@article{faucris.204885732,
abstract = {Generalized pustular psoriasis (GPP) is a potentially life-threatening disease that can be attributed to mutations in IL36RN in a subgroup of patients. In small trials, interleukin (IL)-17A and IL-17RA antagonists have been shown to be effective in patients with generalized pustular psoriasis in Japan. We identified seven patients who received the IL-17A antagonists secukinumab (six cases) or ixekizumab (one case) in two dermatological centers. All patients showed a good or excellent clinical response. Anti-IL-17A therapy was well tolerated and ongoing in all patients after an average therapy duration of 12.9 months. Analysis of IL36RN mutation status was performed in six patients, one patient carried a heterozygous mutation, while the other five patients did not show a mutation in IL36RN. This is the first report of a successful treatment of GPP patients without IL36RN mutations responding to anti-IL-17A therapy.},
author = {Wilsmann-Theis, Dagmar and Schnell, Lisa Marie and Ralser-Isselstein, Veronika and Bieber, Thomas and Schoen, Michael P. and Hüffmeier, Ulrike and Moessner, Rotraut},
doi = {10.1111/1346-8138.14318},
faupublication = {yes},
journal = {Journal of Dermatology},
note = {EVALuna2:34625},
pages = {850-854},
peerreviewed = {Yes},
title = {{Successful} treatment with interleukin-{17A} antagonists of generalized pustular psoriasis in patients without {IL36RN} mutations},
volume = {45},
year = {2018}
}
@article{faucris.211907335,
author = {Regensburger, Martin and Mielenz, Dirk and Winner, Beate},
doi = {10.18632/aging.101431},
faupublication = {yes},
journal = {Aging-Us},
keywords = {Neurodegeneration; Swiprosin-1; EFhd2; Adult neurogenesis},
note = {EVALuna2:35785},
pages = {522-523},
peerreviewed = {No},
title = {{Swiprosin}-1/{EFhd2}-another piece in the puzzle of tauopathy?},
volume = {10},
year = {2018}
}
@article{faucris.204884122,
abstract = {Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare, aggressive RCC type, originally described in the setting of hereditary leiomyomatosis and RCC syndrome, which is defined by germline FH gene inactivation. Inactivation of components of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex is involved in renal medullary carcinoma (SMARCB1/INI1 loss), clear cell RCC (PBRM1 loss), and subsets of dedifferentiated RCC of clear cell, chromophobe, and papillary types (loss of different SWI/SNF components). FH-RCC and SWI/SNF-deficient RCC share anaplastic nuclear features and highly aggressive course. We analyzed 32 FH-RCCs from 28 patients using 7 commercially available SWI/SNF antibodies (SMARCB1/INI1, SMARCA2, SMARCA4, SMARCC1, SMARCC2, PBRM1, and ARID1A). Variable loss of SMARCB1, ARID1A, and SMARCC1 was observed in 1 of 31, 2 of 31, and 1 of 29 evaluable cases, respectively; 3 of these 4 SWI/SNF-deficient tumors had confirmed FH mutations. No correlation of SWI/SNF loss with solid or sarcomatoid features was observed. Two tumors with SMARCB1 and ARID1A deficiency had available SWI/SNF molecular data; both lacked SMARCB1 and ARID1A mutations. The remaining 5 SWI/SNF components were intact in all cases. Especially PBRM1 seems not to be involved in the pathogenesis or progression of FH-RCC. Our data showed that a subset of FH-RCC (12%) have a variable loss of SWI/SNF complex subunits, likely as secondary genetic events. This should not be confused with SWI/SNF-deficient RCC of other types. Evaluation of FH and SWI/SNF together with comprehensive molecular genetic profiling is needed to explore possible prognostic implications of FH/SWI-SNF double deficiency and to better understand the somatic mutation landscape in high-grade RCC.
},
author = {Agaimy, Abbas and Amin, Mahul B. and Gill, Anthony and Popp, Bernt and Reis, André and Berney, Daniel M. and Magi-Galluzzi, Cristina and Sibony, Mathilde and Smith, Steven C. and Suster, Saul and Trpkov, Kiril and Hes, Ondrej and Hartmann, Arndt},
doi = {10.1016/j.humpath.2018.04.004},
faupublication = {yes},
journal = {Human Pathology},
note = {EVALuna2:34610},
pages = {139-146},
peerreviewed = {Yes},
title = {{SWI}/{SNF} protein expression status in fumarate hydratase-deficient renal cell carcinoma: immunohistochemical analysis of 32 tumors from 28 patients},
volume = {77},
year = {2018}
}
@article{faucris.107400524,
abstract = {Multiple system atrophy (MSA), an atypical parkinsonian disorder, is characterized by ?-synuclein (?-syn(+)) cytoplasmatic inclusions in mature oligodendrocytes. Oligodendrocyte progenitor cells (OPCs) represent a distinct cell population with the potential to replace dysfunctional oligodendrocytes. However, the role of OPCs in MSA and their potential to replace mature oligodendrocytes is still unclear. A postmortem analysis in MSA patients revealed ?-syn within OPCs and an increased number of striatal OPCs. In an MSA mouse model, an age-dependent increase of dividing OPCs within the striatum and the cortex was detected. Despite of myelin loss, there was no reduction of mature oligodendrocytes in the corpus callosum or the striatum. Dissecting the underlying molecular mechanisms an oligodendroglial cell line expressing human ?-syn revealed that ?-syn delays OPC maturation by severely downregulating myelin-gene regulatory factor and myelin basic protein. Brain-derived neurotrophic factor was reduced in MSA models and its in vitro supplementation partially restored the phenotype. Taken together, efficacious induction of OPC maturation may open the window to restore glial and neuronal function in MSA.},
author = {May, Verena Elisabeth Luise and Ettle, Benjamin and Pöhler, Anne-Maria and Nuber, Silke and Ubhi, Kiren and Rockenstein, Edward and Winner, Beate and Wegner, Michael and Masliah, Eliezer and Winkler, Jürgen},
doi = {10.1016/j.neurobiolaging.2014.02.028},
faupublication = {yes},
journal = {Neurobiology of Aging},
note = {EVALuna2:4963},
pages = {2357-68},
peerreviewed = {Yes},
title = {?-{Synuclein} impairs oligodendrocyte progenitor maturation in multiple system atrophy},
volume = {35},
year = {2014}
}
@article{faucris.123828144,
abstract = {Multiple system atrophy (MSA) is a rare atypical parkinsonian disorder characterized by a rapidly progressing clinical course and at present without any efficient therapy. Neuropathologically, myelin loss and neurodegeneration are associated with ?-synuclein accumulation in oligodendrocytes, but underlying pathomechanisms are poorly understood. Here, we analyzed the impact of oligodendrocytic ?-synuclein on the formation of myelin sheaths to define a potential interventional target for MSA. Post-mortem analyses of MSA patients and controls were performed to quantify myelin and oligodendrocyte numbers. As pre-clinical models, we used transgenic MSA mice, a myelinating stem cell-derived oligodendrocyte-neuron co-culture, and primary oligodendrocytes to determine functional consequences of oligodendrocytic ?-synuclein overexpression on myelination. We detected myelin loss accompanied by preserved or even increased numbers of oligodendrocytes in post-mortem MSA brains or transgenic mouse forebrains, respectively, indicating an oligodendrocytic dysfunction in myelin formation. Corroborating this observation, overexpression of ?-synuclein in primary and stem cell-derived oligodendrocytes severely impaired myelin formation, defining a novel ?-synuclein-linked pathomechanism in MSA. We used the pro-myelinating activity of the muscarinic acetylcholine receptor antagonist benztropine to analyze the reversibility of the myelination deficit. Transcriptome profiling of primary pre-myelinating oligodendrocytes demonstrated that benztropine readjusts myelination-related processes such as cholesterol and membrane biogenesis, being compromised by oligodendrocytic ?-synuclein. Additionally, benztropine restored the ?-synuclein-induced myelination deficit of stem cell-derived oligodendrocytes. Strikingly, benztropine also ameliorated the myelin deficit in transgenic MSA mice, resulting in a prevention of neuronal cell loss. In conclusion, this study defines the ?-synuclein-induced myelination deficit as a novel and crucial pathomechanism in MSA. Importantly, the reversible nature of this oligodendrocytic dysfunction opens a novel avenue for an intervention in MSA.},
author = {Ettle, Benjamin and Kerman, Bilal E. and Valera, Elvira and Gillmann, Clarissa and Schlachetzki, Johannes and Reiprich, Simone and Büttner, Christian and Ekici, Arif Bülent and Reis, André and Wegner, Michael and Bäuerle, Tobias and Riemenschneider, Markus J. and Masliah, Eliezer and Gage, Fred H. and Winkler, Jürgen},
doi = {10.1007/s00401-016-1572-y},
faupublication = {yes},
journal = {Acta Neuropathologica},
note = {EVALuna2:4991},
pages = {59-75},
peerreviewed = {Yes},
title = {?-{Synuclein}-induced myelination deficit defines a novel interventional target for multiple system atrophy},
volume = {132},
year = {2016}
}
@article{faucris.110892364,
abstract = {Intellectual disability (ID) disorders are genetically and phenotypically extremely heterogeneous. Can this complexity be depicted in a comprehensive way as a means of facilitating the understanding of ID disorders and their underlying biology? We provide a curated database of 746 currently known genes, mutations in which cause ID (ID-associated genes [ID-AGs]), classified according to ID manifestation and associated clinical features. Using this integrated resource, we show that ID-AGs are substantially enriched with co-expression, protein-protein interactions, and specific biological functions. Systematic identification of highly enriched functional themes and phenotypes revealed typical phenotype combinations characterizing process-defined groups of ID disorders, such as chromatin-related disorders and deficiencies in DNA repair. Strikingly, phenotype classification efficiently breaks down ID-AGs into subsets with significantly elevated biological coherence and predictive power. Custom-made functional Drosophila datasets revealed further characteristic phenotypes among ID-AGs and specific clinical classes. Our study and resource provide systematic insights into the molecular and clinical landscape of ID disorders, represent a significant step toward overcoming current limitations in ID research, and prove the utility of systematic human and cross-species phenomics analyses in highly heterogeneous genetic disorders.},
author = {Kochinke, Korinna and Zweier, Christiane and Nijhof, Bonnie and Fenckova, Michaela and Cizek, Pavel and Honti, Frank and Keerthikumar, Shivakumar and Oortveld, Merel A. W. and Kleefstra, Tjitske and Kramer, Jamie M. and Webber, Caleb and Huynen, Martijn A. and Schenck, Annette},
doi = {10.1016/j.ajhg.2015.11.024},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:9318},
pages = {149-64},
peerreviewed = {Yes},
title = {{Systematic} {Phenomics} {Analysis} {Deconvolutes} {Genes} {Mutated} in {Intellectual} {Disability} into {Biologically} {Coherent} {Modules}},
volume = {98},
year = {2016}
}
@article{faucris.240315622,
abstract = {Uterine leiomyomas (ULs) constitute a considerable health burden in the general female population. The fumarate hydratase (FH) deficient subtype is found in up to 1.6% and can occur in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. We sequenced 13 FH deficient ULs from a previous immunohistochemical screen using a targeted panel and identified biallelic FH variants in all. In eight, we found an FH point mutation (two truncating, six missense) with evidence for loss of the second allele. Variant allele-frequencies in all cases with a point mutation pointed to somatic variants. Spatial clustering of the identified missense variants in the lyase domain indicated altered fumarase oligomerization with subsequent degradation as explanation for the observed FH deficiency. Biallelic FH deletions in five tumors confirm the importance of copy number loss as mutational mechanism. By curating all pathogenic FH variants and calculating their population frequency, we estimate a carrier frequency of up to 1/2,563. Comparing with the prevalence of FH deficient ULs, we conclude that most are sporadic and estimate 2.7–13.9% of females with an FH deficient UL to carry a germline FH variant. Further prospective tumor/normal sequencing studies are needed to develop a reliable screening strategy for HLRCC in women with ULs.},
author = {Popp, Bernt and Erber, Ramona and Kraus, Cornelia and Vasileiou, Georgia and Hoyer, Juliane and Burghaus, Stefanie and Hartmann, Arndt and Beckmann, Matthias and Reis, André and Agaimy, Abbas},
doi = {10.1038/s41379-020-0596-y},
faupublication = {yes},
journal = {Modern Pathology},
note = {CRIS-Team Scopus Importer:2020-07-10},
peerreviewed = {Yes},
title = {{Targeted} sequencing of {FH}-deficient uterine leiomyomas reveals biallelic inactivating somatic fumarase variants and allows characterization of missense variants},
year = {2020}
}
@article{faucris.252912776,
abstract = {Progress in the field of neurogenesis is limited by the lack of animal models allowing direct detection and analysis of living cells participating in neurogenesis. We engineered a transgenic mouse model that expresses the fluorescent reporter proteins enhanced green fluorescent protein or Discoma sp. reef coral red fluorescent protein under the control of the doublecortin (DCX) promoter, a gene specifically and transiently active in neuronal precursors and young neurons. The expression of the reporter proteins correlated with expression of the endogenous DCX protein, and with developmental and adult neurogenesis. Neurogenesis was unaffected by the presence of the fluorescent proteins. The transgenic mice allowed direct identification of the very few newly generated neurons present in the aged brain. We performed electrophysiological analysis and established that newly generated hippocampal granule cells in aged and young mice shared identical physiological properties. Hence, although the rate of neurogenesis tapers with ageing, a population of highly excitable young neurons indistinguishable to those found in younger animals is continuously generated. Therefore, maintenance of the fundamental properties of neuronal precursors even at advanced age suggests that stimulation of neurogenesis may constitute a valid strategy to counteract age-related neuronal loss and cognitive declines.},
author = {Winner, Beate and Bogdahn, Ulrich and Winkler, Jürgen and et al.},
author_hint = {Couillard-Despres, Winner, Karl, Lindemann, Schmid, Aigner, Laemke, Bogdahn, Winkler, Bischofberger, Aigner},
doi = {10.1111/j.1460-9568.2006.05039.x},
faupublication = {no},
journal = {European Journal of Neuroscience},
pages = {1535-45},
peerreviewed = {Yes},
support_note = {Author relations incomplete. You may find additional data in field 'author{\_}hint'},
title = {{Targeted} transgene expression in neuronal precursors: watching young neurons in the old brain.},
volume = {24},
year = {2006}
}
@article{faucris.215448950,
abstract = {The TCF4 gene encodes for the basic helix-loop-helix transcription factor 4 (TCF4), which plays an important role in the development of the central nervous system (CNS). Haploinsufficiency of TCF4 was found to cause Pitt-Hopkins syndrome (PTHS), a severe neurodevelopmental disorder. Recently, the screening of a large cohort of medulloblastoma (MB), a highly aggressive embryonal brain tumor, revealed almost 20% of adult patients with MB of the Sonic hedgehog (SHH) subtype carrying somatic TCF4 mutations. Interestingly, many of these mutations have previously been detected as germline mutations in patients with PTHS. We show here that overexpression of wild-type TCF4 in vitro significantly suppresses cell proliferation in MB cells, whereas mutant TCF4 proteins do not to the same extent. Furthermore, RNA sequencing revealed significant upregulation of multiple well-known tumor suppressors upon expression of wild-type TCF4. In vivo, a prenatal knockout of Tcf4 in mice caused a significant increase in apoptosis accompanied by a decreased proliferation and failed migration of cerebellar granule neuron precursor cells (CGNP), which are thought to be the cells of origin for SHH MB. In contrast, postnatal in vitro and in vivo knockouts of Tcf4 with and without an additional constitutive activation of the SHH pathway led to significantly increased proliferation of CGNP or MB cells. Finally, publicly available data from human MB show that relatively low expression levels of TCF4 significantly correlate with a worse clinical outcome. These results not only point to time-specific roles of Tcf4 during cerebellar development but also suggest a functional linkage between TCF4 mutations and the formation of SHH MB, proposing that TCF4 acts as a tumor suppressor during postnatal stages of cerebellar development.},
author = {Hellwig, Malte and Lauffer, Marlen C. and Bockmayr, Michael and Spohn, Michael and Merk, Daniel J. and Harrison, Luke and Ahlfeld, Julia and Kitowski, Annabel and Neumann, Julia E. and Ohli, Jasmin and Holdhof, Doerthe and Niesen, Judith and Schoof, Melanie and Kool, Marcel and Kraus, Cornelia and Zweier, Christiane and Holmberg, Dan and Schueller, Ulrich},
doi = {10.1007/s00401-019-01982-5},
faupublication = {yes},
journal = {Acta Neuropathologica},
note = {CRIS-Team WoS Importer:2019-04-04},
pages = {657-673},
peerreviewed = {Yes},
title = {{TCF4} ({E2}-2) harbors tumor suppressive functions in {SHH} medulloblastoma},
volume = {137},
year = {2019}
}
@inproceedings{faucris.248095540,
address = {LONDON},
author = {Krumbiegel, Mandy and Trollmann, Regina and Mammadova, Dilbar and Schnell, Alexander and Kraus, Cornelia and Ekici, Arif Bülent and Reis, André and Zweier, Christiane},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {588-588},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Tetrasomy} of {SCN2A} associated with refractory neonatal epileptic encephalopathy},
year = {2020}
}
@article{faucris.215694239,
abstract = {Introduction: Parkinson's disease (PD) is the most common neurodegenerative movement disorder caused by the progressive loss of neurons in the midbrain and other brain regions. Only symptomatic treatment is currently available. Mounting evidence suggests that T cells are a key contributor to PD pathogenesis and neurodegeneration by a mechanism that requires further elucidation. Areas covered: We discuss the evidence of imbalanced activation of effector T cell populations in PD and summarize the data of Th17 involvement and Th17-regulated mechanisms in PD pathology. Moreover, possible Th17-related molecular targets as possible neuroprotective immunomodulatory therapeutic targets for PD are examined. Expert Opinion: Existing data show that Th17 cells, their effector molecules, and signaling pathways are potentially effective therapeutic targets for neuroprotective immunomodulation in PD treatment. However, specificity of action within Th17-mediated signaling pathways for PD requires careful consideration.},
author = {Prots, Iryna and Winner, Beate},
doi = {10.1080/14728222.2019.1590336},
faupublication = {yes},
journal = {Expert Opinion on Therapeutic Targets},
keywords = {T cells; Th17 cells; neurodegeneration; Parkinson’s disease; IL-6; IL-1β},
note = {CRIS-Team WoS Importer:2019-04-09},
pages = {309-314},
peerreviewed = {Yes},
title = {{Th17} cells: a promising therapeutic target for {Parkinson}'s disease?},
volume = {23},
year = {2019}
}
@article{faucris.234565376,
author = {Sommer, Annika and Marxreiter, Franz and Krach, Florian and Fadler, Tanja and Grosch, Janina and Maroni, Michele and Gräf, Daniela and Eberhardt, Esther and Riemenschneider, Markus J. and Yeo, Gene W. and Kohl, Zacharias and Xiang, Wei and Gage, Fred H. and Winkler, Jürgen and Prots, Iryna and Winner, Beate},
doi = {10.1016/j.stem.2019.04.019},
faupublication = {yes},
journal = {Cell Stem Cell},
note = {EVALuna2:203042},
pages = {10061006},
peerreviewed = {No},
title = {{Th17} {Lymphocytes} {Induce} {Neuronal} {Cell} {Death} in a {Human} {iPSC}-{Based} {Model} of {Parkinson}'s {Disease}},
volume = {24},
year = {2019}
}
@article{faucris.211478893,
abstract = {Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of midbrain neurons (MBNs). Recent evidence suggests contribution of the adaptive immune system in PD. Here, we show a role for human T lymphocytes as cell death inducers of induced pluripotent stem cell (iPSC)-derived MBNs in sporadic PD. Higher Th17 frequencies were found in the blood of PD patients and increased numbers of T lymphocytes were detected in postmortem PD brain tissues. We modeled this finding using autologous co-cultures of activated T lymphocytes and iPSC-derived MBNs of sporadic PD patients and controls. After co-culture with T lymphocytes or the addition of IL-17, PD iPSC-derived MBNs underwent increased neuronal death driven by upregulation of IL-17 receptor (IL-17R) and NF kappa B activation. Blockage of IL-17 or IL-17R, or the addition of the FDA-approved anti-IL-17 antibody, secukinumab, rescued the neuronal death. Our findings indicate a critical role for IL-17-producing T lymphocytes in sporadic PD.},
author = {Sommer, Annika and Maxreiter, Franz and Krach, Florian and Fadler, Tanja and Grosch, Janina and Maroni, Michele and Graef, Daniela and Eberhardt, Esther and Riemenschneider, Markus J. and Yeo, Gene W. and Kohl, Zacharias and Xiang, Wei and Gage, Fred H. and Winkler, Jürgen and Prots, Iryna and Winner, Beate},
doi = {10.1016/j.stem.2018.06.015},
faupublication = {yes},
journal = {Cell Stem Cell},
note = {EVALuna2:35782},
pages = {123-+},
peerreviewed = {Yes},
title = {{Th17} {Lymphocytes} {Induce} {Neuronal} {Cell} {Death} in a {Human} {iPSC}-{Based} {Model} of {Parkinson}'s {Disease}},
volume = {23},
year = {2018}
}
@article{faucris.281181846,
abstract = {Th2 cells provide effector functions in type 2 immune responses to helminths and allergens. Despite knowledge about molecular mechanisms of Th2 cell differentiation, there is little information on Th2 cell heterogeneity and clonal distribution between organs. To address this, we performed combined single-cell transcriptome and T-cell receptor (TCR) clonotype analysis on murine Th2 cells in mesenteric lymph nodes (MLNs) and lung after infection with Nippostrongylus brasiliensis (Nb) as a human hookworm infection model. We find organ-specific expression profiles, but also populations with conserved migration or effector/resident memory signatures that unexpectedly cluster with potentially regulatory Il10(pos)Foxp3(neg) cells. A substantial MLN subpopulation with an interferon response signature suggests a role for interferon signaling in Th2 differentiation or diversification. Further RNA-inferred developmental directions indicate proliferation as a hub for differentiation decisions. Although the TCR repertoire is highly heterogeneous, we identified expanded clones and CDR3 motifs. Clonal relatedness between distant organs confirmed effective exchange of Th2 effector cells, although locally expanded clones dominated the response. We further cloned an Nb-specific TCR from an expanded clone in the lung effector cluster and describe surface markers that distinguish transcriptionally defined clusters. These results provide insights in Th2 cell subset diversity and clonal relatedness in distant organs.},
author = {Radtke, Daniel and Thuma, Natalie and Schülein, Christine and Kirchner, Philipp and Ekici, Arif Bülent and Schober, Kilian and Vöhringer, David},
doi = {10.7554/eLife.74183},
faupublication = {yes},
journal = {eLife},
note = {CRIS-Team WoS Importer:2022-09-02},
peerreviewed = {Yes},
title = {{Th2} single-cell heterogeneity and clonal distribution at distant sites in helminth-infected mice},
volume = {11},
year = {2022}
}
@article{faucris.256243608,
author = {Genzel-Boroviczeny, Orsolya and Bannasch, Thomas and Baeuml, Josef and Friedrich, Orsolya and Hellemann, Joachim and Kress, Wolfram and Magdefrau, Carola and Manzeschke, Arne and Pettinger, Joseph and Pogarell, Oliver and Rieger-Fackeldey, Esther and Robin, Dunja and Rogenhofer, Nina and Schlund, Gerhardt H. and Zweier, Christiane and Zollner, Ursula},
doi = {10.3238/arztebl.m2021.0005},
faupublication = {yes},
journal = {Deutsches Ärzteblatt international},
month = {Jan},
note = {CRIS-Team WoS Importer:2021-04-23},
pages = {37-38},
peerreviewed = {No},
title = {{The} {Bavarian} {Ethics} {Committee} for {Pre}-{Implantation} {Diagnosis}-811 {Decisions} {Over} 5 {Years}},
volume = {118},
year = {2021}
}
@article{faucris.212601926,
author = {Wolff, Dorit and Feldt, Torsten and Reifenberger, Julia and Sebald, Heidi and Bogdan, Christian},
doi = {10.1128/JCM.01958-17},
faupublication = {yes},
journal = {Journal of Clinical Microbiology},
note = {EVALuna2:36422},
peerreviewed = {No},
title = {{The} {Brief} {Case}: {Cutaneous} {Sporotrichosis} in an {Immunocompetent} {Patient} after {Travel} to {Peru}},
volume = {56},
year = {2018}
}
@article{faucris.107413724,
abstract = {Swiprosin-1/EFhd2 (EFhd2) is a cytoskeletal Ca2+ sensor protein strongly expressed in the brain. It has been shown to interact with mutant tau, which can promote neurodegeneration, but nothing is known about the physiological function of EFhd2 in the nervous system. To elucidate this question, we analyzed EFhd2-/-/lacZ reporter mice and showed that lacZ was strongly expressed in the cortex, the dentate gyrus, the CA1 and CA2 regions of the hippocampus, the thalamus, and the olfactory bulb. Immunohistochemistry and western blotting confirmed this pattern and revealed expression of EFhd2 during neuronal maturation. In cortical neurons, EFhd2 was detected in neurites marked by MAP2 and co-localized with pre- and post-synaptic markers. Approximately one third of EFhd2 associated with a biochemically isolated synaptosome preparation. There, EFhd2 was mostly confined to the cytosolic and plasma membrane fractions. Both synaptic endocytosis and exocytosis in primary hippocampal EFhd2-/- neurons were unaltered but transport of synaptophysin-GFP containing vesicles was enhanced in EFhd2-/- primary hippocampal neurons, and notably, EFhd2 inhibited kinesin mediated microtubule gliding. Therefore, we found that EFhd2 is a neuronal protein that interferes with kinesin-mediated transport.},
author = {Purohit, Pavitra and Perez-Branguli, Francesc and Prots, Iryna and Borger, Eva and Gunn-Moore, Frank and Welzel, Oliver and Loy, Kristina and Wenzel, Eva Maria and Groemer, Teja W. and Brachs, Sebastian and Holzer, Max and Buslei, Rolf and Fritsch, Kristin and Regensburger, Martin and Boehm, Konrad J. and Winner, Beate and Mielenz, Dirk},
doi = {10.1371/journal.pone.0103976},
faupublication = {yes},
journal = {PLoS ONE},
note = {EVALuna2:7246},
pages = {e103976},
peerreviewed = {Yes},
title = {{The} {Ca2}+ sensor protein swiprosin-1/{EFhd2} is present in neurites and involved in kinesin-mediated transport in neurons},
volume = {9},
year = {2014}
}
@article{faucris.110781044,
author = {Sonntag, Daniel and Tresp, Volker and Zillner, Sonja and Hammon, Matthias and Reis, André and Fasching, Peter and Sedlmayr, Martin and Ganslandt, Thomas and Prokosch, Hans-Ulrich and Budde, Clemens and Schmidt, Danilo and Hinrichs, Carl and Wittenberg, Thomas and Daumcke, Philipp and Oppelt, Patricia and Cavallaro, Alexander Josef},
doi = {10.1007/s00287-015-0913-x},
faupublication = {yes},
journal = {Informatik-Spektrum},
note = {UnivIS-Import:2017-12-18:Pub.2015.tech.IMMD.infome.thecli},
pages = {1-11},
peerreviewed = {Yes},
title = {{The} clinical data intelligence project},
url = {http://link.springer.com/article/10.1007/s00287-015-0913-x},
volume = {ePub},
year = {2015}
}
@article{faucris.106421744,
abstract = {Despite abundant evidence for pathogenicity of large copy number variants (CNVs) in neurodevelopmental disorders (NDDs), the individual significance of genome-wide rare CNVs <500 kb has not been well elucidated in a clinical context.By high-resolution chromosomal microarray analysis, we investigated the clinical significance of all rare non-polymorphic exonic CNVs sizing 1-500 kb in a cohort of 714 patients with undiagnosed NDDs.We detected 96 rare CNVs <500 kb affecting coding regions, of which 58 (60.4%) were confirmed. 6 of 14 confirmed de novo, one of two homozygous and four heterozygous inherited CNVs affected the known microdeletion regions 17q21.31, 16p11.2 and 2p21 or OMIM morbid genes (CASK, CREBBP, PAFAH1B1, SATB2; AUTS2, NRXN3, GRM8). Two further de novo CNVs affecting single genes (MED13L, CTNND2) were instrumental in delineating novel recurrent conditions. For the first time, we here report exonic deletions of CTNND2 causing low normal IQ with learning difficulties with or without autism spectrum disorder. Additionally, we discovered a homozygous out-of-frame deletion of ACOT7 associated with features comparable to the published mouse model. In total, 24.1% of the confirmed small CNVs were categorised as pathogenic or likely pathogenic (median size 130 kb), 17.2% as likely benign, 3.4% represented incidental findings and 55.2% remained unclear.These results verify the diagnostic relevance of genome-wide rare CNVs <500 kb, which were found pathogenic in ~2% (14/714) of cases (1.1% de novo, 0.3% homozygous, 0.6% inherited) and highlight their inherent potential for discovery of new conditions.},
author = {Asadollahi, Reza and Oneda, Beatrice and Joset, Pascal and Azzarello-Burri, Silvia and Bartholdi, Deborah and Steindl, Katharina and Vincent, Marie and Cobilanschi, Joana and Sticht, Heinrich and Baldinger, Rosa and Reissmann, Regina and Sudholt, Irene and Thiel, Christian and Ekici, Arif Bülent and Reis, André and Bijlsma, Emilia K. and Andrieux, Joris and Dieux, Anne and Fitzpatrick, David and Ritter, Susanne and Baumer, Alessandra and Latal, Beatrice and Plecko, Barbara and Jenni, Oskar G. and Rauch, Anita},
doi = {10.1136/jmedgenet-2014-102588},
faupublication = {yes},
journal = {Journal of Medical Genetics},
note = {EVALuna2:9237},
pages = {677-88},
peerreviewed = {Yes},
title = {{The} clinical significance of small copy number variants in neurodevelopmental disorders},
volume = {51},
year = {2014}
}
@article{faucris.263251047,
abstract = {The gut–brain axis is a bidirectional communication system driven by neural, hormonal, metabolic, immunological, and microbial signals. Signaling events from the gut can modulate brain function and recent evidence suggests that the gut–brain axis may play a pivotal role in linking gastrointestinal and neurological diseases. Accordingly, accumulating evidence has suggested a link between inflammatory bowel diseases (IBDs) and neurodegenerative, as well as neuroinflammatory diseases. In this context, clinical, epidemiological and experimental data have demonstrated that IBD predisposes a person to pathologies of the central nervous system (CNS). Likewise, a number of neurological disorders are associated with changes in the intestinal environment, which are indicative for disease-mediated gut–brain inter-organ communication. Although this axis was identified more than 20 years ago, the sequence of events and underlying molecular mechanisms are poorly defined. The emergence of precision medicine has uncovered the need to take into account non-intestinal symptoms in the context of IBD that could offer the opportunity to tailor therapies to individual patients. The aim of this review is to highlight recent findings supporting the clinical and biological link between the gut and brain, as well as its clinical significance for IBD as well as neurodegeneration and neuroinflammation. Finally, we focus on novel human-specific preclinical models that will help uncover disease mechanisms to better understand and modulate the function of this complex system.},
author = {Günther, Claudia and Rothhammer, Veit and Karow, Marisa and Neurath, Markus and Winner, Beate},
doi = {10.3390/ijms22168870},
faupublication = {yes},
journal = {International Journal of Molecular Sciences},
keywords = {Ex vivo organ models; Gut-brain axis; IBD; MS; PD},
note = {CRIS-Team Scopus Importer:2021-08-27},
peerreviewed = {Yes},
title = {{The} gut-brain axis in inflammatory bowel disease—current and future perspectives},
volume = {22},
year = {2021}
}
@article{faucris.283988203,
abstract = {Inflammatory bowel disease (IBD) comprises Crohn’s disease (CD) and ulcerative colitis (UC) and is associated with neuropsychiatric symptoms like anxiety and depression. Both conditions strongly worsen IBD disease burden. In the present review, we summarize the current understanding of the pathogenesis of depression and anxiety in IBD. We present a stepwise cascade along a gut–immune–brain axis initiated by evasion of chronic intestinal inflammation to pass the epithelial and vascular barrier in the gut and cause systemic inflammation. We then summarize different anatomical transmission routes of gut-derived peripheral inflammation into the central nervous system (CNS) and highlight the current knowledge on neuroinflammatory changes in the CNS of preclinical IBD mouse models with a focus on microglia, the brain-resident macrophages. Subsequently, we discuss how neuroinflammation in IBD can alter neuronal circuitry to trigger symptoms like depression and anxiety. Finally, the role of intestinal microbiota in the gut–immune–brain axis in IBD will be reviewed. A more comprehensive understanding of the interaction between the gastrointestinal tract, the immune system and the CNS accounting for the similarities and differences between UC and CD will pave the path for improved prediction and treatment of neuropsychiatric comorbidities in IBD and other inflammatory diseases.},
author = {Masanetz, Rebecca Katharina and Winkler, Jürgen and Winner, Beate and Günther, Claudia and Süß, Patrick},
doi = {10.3390/ijms231911111},
faupublication = {yes},
journal = {International Journal of Molecular Sciences},
keywords = {Crohn’s disease; depression; gut microbiota; gut-brain axis; inflammatory bowel disease; neuroinflammation; systemic inflammation; ulcerative colitis},
note = {Created from Fastlane, Scopus look-up},
peerreviewed = {Yes},
title = {{The} {Gut}–{Immune}–{Brain} {Axis}: {An} {Important} {Route} for {Neuropsychiatric} {Morbidity} in {Inflammatory} {Bowel} {Disease}},
volume = {23},
year = {2022}
}
@article{faucris.204886657,
abstract = {Eleven-nineteen leukemia (ENL) is a chromatin reader present in complexes stimulating transcriptional elongation. It is fused to mixed-lineage leukemia (MLL) in leukemia, and missense mutations have been identified in Wilms tumor and acute myeloid leukemia. Here we demonstrate that ENL overcomes polycomb silencing through recruitment of PAF1 via the conserved YEATS domain, which recognizes acetylated histone H3. PAF1 was responsible for antirepressive activities of ENL in vitro, and it determined the transforming potential of MLL-ENL. MLL-ENL target loci showed supraphysiological PAF1 binding, hyperubiquitination of histone H2B and hypomodification with H2AUb, resulting in accelerated transcription rates. YEATS mutations induced a gain of function, transforming primary hematopoietic cells in vitro and in transplantation assays through aberrant transcription and H2B ubiquitination of Hoxa9 and Meis1 Mechanistically, H3 and PAF1 competed for ENL interaction, with activating mutations favoring PAF1 binding, whereas the MLL moiety provided a constitutive PAF1 tether allowing MLL fusions to circumvent H3 competition.
},
author = {Hetzner, Katrin and Garcia-Cuellar, Maria-Paz and Büttner, Christian and Slany, Robert},
doi = {10.1182/blood-2017-11-815035},
faupublication = {yes},
journal = {Blood},
note = {EVALuna2:34633},
pages = {662-673},
peerreviewed = {Yes},
title = {{The} interaction of {ENL} with {PAF1} mitigates polycomb silencing and facilitates murine leukemogenesis},
volume = {131},
year = {2018}
}
@article{faucris.211825736,
abstract = {BackgroundThe TUBA1A-associated tubulinopathy is clinically heterogeneous with brain malformations, microcephaly, developmental delay and epilepsy being the main clinical features. It is an autosomal dominant disorder mostly caused by de novo variants in TUBA1A.ResultsIn three individuals with developmental delay we identified heterozygous de novo missense variants in TUBA1A using exome sequencing. While the c.1307G>A, p.(Gly436Asp) variant was novel, the two variants c.518C>T, p.(Pro173Leu) and c.641G>A, p.(Arg214His) were previously described. We compared the variable phenotype observed in these individuals with a carefully conducted review of the current literature and identified 166 individuals, 146 born and 20 fetuses with a TUBA1A variant. In 107 cases with available clinical information we standardized the reported phenotypes according to the Human Phenotype Ontology. The most commonly reported features were developmental delay (98%), anomalies of the corpus callosum (96%), microcephaly (76%) and lissencephaly (agyria-pachygyria) (70%), although reporting was incomplete in the different studies. We identified a total of 121 specific variants, including 15 recurrent ones. Missense variants cluster in the C-terminal region around the most commonly affected amino acid position Arg402 (13.3%). In a three-dimensional protein model, 38.6% of all disease-causing variants including those in the C-terminal region are predicted to affect the binding of microtubule-associated proteins or motor proteins. Genotype-phenotype analysis for recurrent variants showed an overrepresentation of certain clinical features. However, individuals with these variants are often reported in the same publication.ConclusionsWith 166 individuals, we present the most comprehensive phenotypic and genotypic standardized synopsis for clinical interpretation of TUBA1A variants. Despite this considerable number, a detailed genotype-phenotype characterization is limited by large inter-study variability in reporting.},
author = {Hebebrand, Moritz and Hüffmeier, Ulrike and Trollmann, Regina and Hehr, Ute and Uebe, Steffen and Ekici, Arif Bülent and Kraus, Cornelia and Krumbiegel, Mandy and Reis, André and Thiel, Christian and Popp, Bernt},
doi = {10.1186/s13023-019-1020-x},
faupublication = {yes},
journal = {Orphanet Journal of Rare Diseases},
note = {CRIS-Team WoS Importer:2019-02-27},
peerreviewed = {Yes},
title = {{The} mutational and phenotypic spectrum of {TUBA1A}-associated tubulinopathy},
volume = {14},
year = {2019}
}
@article{faucris.111765984,
abstract = {Microglia cells fulfill key homeostatic functions and essentially contribute to host defense within the CNS. Altered activation of microglia, in turn, has been implicated in neuroinflammatory and neurodegenerative diseases. In this study, we identify the nuclear receptor (NR) Nr4a1 as key rheostat controlling the activation threshold and polarization of microglia. In steady-state microglia, ubiquitous neuronal-derived stress signals such as ATP induced expression of this NR, which contributed to the maintenance of a resting and noninflammatory microglia phenotype. Global and microglia-specific deletion of Nr4a1 triggered the spontaneous and overwhelming activation of microglia and resulted in increased cytokine and NO production as well as in an accelerated and exacerbated form of experimental autoimmune encephalomyelitis. Ligand-induced activation of Nr4a1 accordingly ameliorated the course of this disease. Our current data thus identify Nr4a1 as regulator of microglia activation and potentially new target for the treatment of inflammatory CNS diseases such as multiple sclerosis.},
author = {Rothe, Tobias and Ipseiz, Natacha and Faas, Maria and Lang, Stefanie and Perez-Branguli, Francesc and Metzger, Daniel and Ichinose, Hiroshi and Winner, Beate and Schett, Georg and Krönke, Gerhard},
doi = {10.4049/jimmunol.1600638},
faupublication = {yes},
journal = {Journal of Immunology},
note = {EVALuna2:13374},
peerreviewed = {Yes},
title = {{The} {Nuclear} {Receptor} {Nr4a1} {Acts} as a {Microglia} {Rheostat} and {Serves} as a {Therapeutic} {Target} in {Autoimmune}-{Driven} {Central} {Nervous} {System} {Inflammation}},
year = {2017}
}
@article{faucris.209558826,
abstract = {Charcot-Marie-Tooth disease (CMT) represents a heterogeneous group of hereditary peripheral neuropathies. We previously reported a CMT locus on chromosome 19q13.3 segregating with the disease in a large Costa Rican family with axonal neuropathy and autosomal recessive pattern of inheritance (CMT2B2). We proposed a homozygous missense variant in the Mediator complex 25 (MED25) gene as causative of the disease. Nevertheless, the fact that no other CMT individuals with MED25 variants were reported to date led us to reevaluate the original family. Using exome sequencing, we now identified a homozygous nonsense variant (p.Gln517ter) in the last exon of an adjacent gene, the polynucleotide kinase 3'-phosphatase (PNKP) gene. It encodes a DNA repair protein recently associated with recessive ataxia with oculomotor apraxia type 4 (AOA4) and microcephaly, seizures, and developmental delay (MCSZ). Subsequently, five unrelated Costa Rican CMT2 subjects initially identified as being heterozygous for the same MED25 variant were found to be also compound heterozygote for PNKP. All were heterozygous for the same variant found homozygous in the large family and a second one previously associated with ataxia (p.Thr408del). Detailed clinical reassessment of the initial family and the new individuals revealed in all an adult-onset slowly progressive CMT2 associated with signs of cerebellar dysfunction such as slurred speech and oculomotor involvement, but neither microcephaly, seizures, nor developmental delay. We propose that PKNP variants are the major causative variant for the CMT2 phenotype in these individuals and that the milder clinical manifestation is due to an allelic effect.
},
author = {Leal, Alejandro and Bogantes-Ledezma, Sixto and Ekici, Arif Bülent and Uebe, Steffen and Thiel, Christian and Sticht, Heinrich and Berghoff, Martin and Berghoff, Corinna and Morera, Bernal and Meisterernst, Michael and Reis, André},
doi = {10.1007/s10048-018-0555-7},
faupublication = {yes},
journal = {Neurogenetics},
note = {EVALuna2:35117},
pages = {215-225},
peerreviewed = {Yes},
title = {{The} polynucleotide kinase 3'-phosphatase gene ({PNKP}) is involved in {Charcot}-{Marie}-{Tooth} disease ({CMT2B2}) previously related to {MED25}},
volume = {19},
year = {2018}
}
@article{faucris.106126504,
abstract = {The stimulatory effects of CRP (C-reactive protein) on endothelial cells are mainly mediated via Fc?RIIa. This receptor exists in two different allotypes bearing either arginine (R131) or histidine (H131) at the extracellular amino acid position 131 of the mature protein, but only Fc?RIIa-R131 displays high avidity for CRP. This study investigated the role of the Fc?RIIa genotype in CRP-stimulated endothelial cells.We tested the effects of CRP on expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin, as well as the endothelial release of pro-inflammatory molecules as a function of the Fc?RIIa-genotype (Fc?RIIa-H/H131, Fc?RIIa-H/R131, Fc?RIIa-R/R131) in HUVEC (Human Umbilical Vein Endothelial Cells). HUVEC were grouped according to their Fc?RIIa status by genotyping with an allele specific nested-PCR. The expression of ICAM-1, VCAM-1, and E-selectin on HUVEC was detected by flow cytometry. The release of soluble markers (sCD40L, IL-6, IL-8, MCP-1, tPA, sP-selectin, and sVCAM-1) was measured using a multiplex assay for flow cytometry.CRP-stimulated expression of ICAM-1 and E-selectin was dependent on the specific Fc?RIIa-genotype, with most pronounced induction in HUVEC with the Fc?RIIa-R/R genotype, followed by H/R and H/H. In accordance with this finding, the supernatants of stimulated HUVEC with the R/R genotype showed significantly higher levels of tPA, MCP-1, and IL-6. Our data show that CRP stimulates the expression of adhesion molecules and the release of soluble markers by HUVEC as a function of the Fc?RIIa-genotype. These findings could be relevant in the context of risk stratification in patients with cardiovascular disease.},
author = {Raaz-Schrauder, Dorette and Ekici, Arif Bülent and Klinghammer, Lutz and Stumpf, Christian and Achenbach, Stephan and Herrmann, Martin and Reis, André and Garlichs, Christoph},
doi = {10.1016/j.thromres.2013.12.030},
faupublication = {yes},
journal = {Thrombosis Research},
note = {EVALuna2:9209},
pages = {426-32},
peerreviewed = {Yes},
title = {{The} proinflammatory effect of {C}-reactive protein on human endothelial cells depends on the {Fc}?{RIIa} genotype},
volume = {133},
year = {2014}
}
@article{faucris.229010222,
abstract = {LOXL1 (lysyl oxidase-like 1) has been identified as the major effect locus in pseudoexfoliation (PEX) syndrome, a fibrotic disorder of the extracellular matrix and frequent cause of chronic open-angle glaucoma. However, all known PEX-associated common variants show allele effect reversal in populations of different ancestry, casting doubt on their biological significance. Based on extensive LOXL1 deep sequencing, we report here the identification of a common non-coding sequence variant, rs7173049A>G, located downstream of LOXL1, consistently associated with a decrease in PEX risk (odds ratio, OR=0.63; P=6.33x10(-31)) in nine different ethnic populations. We provide experimental evidence for a functional enhancer-like regulatory activity of the genomic region surrounding rs7173049 influencing expression levels of ISLR2 (immunoglobulin superfamily containing leucine-rich repeat protein 2) and STRA6 [stimulated by retinoic acid (RA) receptor 6], apparently mediated by allele-specific binding of the transcription factor thyroid hormone receptor beta. We further show that the protective rs7173049-G allele correlates with increased tissue expression levels of ISLR2 and STRA6 and that both genes are significantly downregulated in tissues of PEX patients together with other key components of the STRA6 receptor-driven RA signaling pathway. siRNA-mediated downregulation of RA signaling induces upregulation of LOXL1 and PEX-associated matrix genes in PEX-relevant cell types. These data indicate that dysregulation of STRA6 and impaired retinoid metabolism are involved in the pathophysiology of PEX syndrome and that the variant rs7173049-G, which represents the first common variant at the broad LOXL1 locus without allele effect reversal, mediates a protective effect through upregulation of STRA6 in ocular tissues.},
author = {Berner, Daniel and Hoja, Ursula and Zenkel, Matthias and Ross, James Julian and Uebe, Steffen and Paoli, Daniela and Frezzotti, Paolo and Rautenbach, Robyn M. and Ziskind, Ari and Williams, Susan E. and Carmichael, Trevor R. and Ramsay, Michele and Topouzis, Fotis and Chatzikyriakidou, Anthi and Lambropoulos, Alexandros and Sundaresan, Periasamy and Ayub, Humaira and Akhtar, Farah and Qamar, Raheel and Zenteno, Juan C. and Cruz-Aguilar, Marisa and Astakhov, Yury S. and Dubina, Michael and Wiggs, Janey and Ozaki, Mineo and Kruse, Friedrich and Aung, Tin and Reis, André and Khor, Chiea Chuen and Pasutto, Francesca and Schlötzer-Schrehardt, Ursula},
doi = {10.1093/hmg/ddz075},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {CRIS-Team WoS Importer:2019-11-12},
pages = {2531-2548},
peerreviewed = {Yes},
title = {{The} protective variant rs7173049 at {LOXL1} locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome},
volume = {28},
year = {2019}
}
@article{faucris.280025515,
abstract = {The accumulation of alpha-synuclein (aSyn) is the hallmark of a group of
neurodegenerative conditions termed synucleopathies. Physiological
functions of aSyn, including those outside of the CNS, remain elusive.
However, a reliable and reproducible evaluation of aSyn protein
expression in different cell types and especially in low-expressing
cells is impeded by the existence of a huge variety of poorly
characterized anti-aSyn antibodies and a lack of a routinely used
sensitive detection methods. Here, we developed a robust flow
cytometry-based workflow for aSyn detection and antibody validation. We
test our workflow using three commercially available antibodies (MJFR1,
LB509, and 2A7) in a variety of human cell types, including induced
pluripotent stem cells, T lymphocytes, and fibroblasts, and provide a
cell- and antibody-specific map for aSyn expression. Strikingly, we
demonstrate a previously unobserved unspecificity of the LB509 antibody,
while the MJFR1 clone revealed specific aSyn binding however with low
sensitivity. On the other hand, we identified an aSyn-specific antibody
clone 2A7 with an optimal sensitivity for detecting aSyn in a range of
cell types, including those with low aSyn expression. We further utilize
our workflow to demonstrate the ability of the 2A7 antibody to
distinguish between physiological differences in aSyn expression in
neuronal and non-neuronal cells from the cortical organoids, and in
neural progenitors and midbrain dopaminergic neurons from healthy
controls and in patients with Parkinson's disease who have aSyn gene
locus duplication. Our results provide a proof of principle for the use
of high-throughput flow cytometry-based analysis of aSyn and highlight
the necessity of rigorous aSyn antibody validation to facilitate the
research of aSyn physiology and patholog},
author = {Leupold, Lukas and Sigutova, Veronika and Gerasimova, Elizaveta and Regensburger, Martin and Zundler, Sebastian and Zunke, Friederike and Xiang, Wei and Winner, Beate and Prots, Iryna},
doi = {10.3389/fneur.2022.869103},
faupublication = {yes},
journal = {Frontiers in Neurology},
keywords = {alpha-synuclein; antibodies; synuclein antibodies; T cell; antibody specificity; flow cytometry; α-synuclein expression},
peerreviewed = {Yes},
title = {{The} {Quest} for {Anti}-α-{Synuclein} {Antibody} {Specificity}—{Lessons} {Learnt} {From} {Flow} {Cytometry} {Analysis}},
volume = {13},
year = {2022}
}
@article{faucris.264590728,
abstract = {Pathogenic variants in aminoacyl-tRNA synthetases (ARS1) cause a diverse spectrum of autosomal recessive disorders. Tyrosyl tRNA synthetase (TyrRS) is encoded by YARS1 (cytosolic, OMIM*603,623) and is responsible of coupling tyrosine to its specific tRNA. Next to the enzymatic domain, TyrRS has two additional functional domains (N-Terminal TyrRS(Mini) and C-terminal EMAP-II-like domain) which confer cytokine-like functions. Mutations in YARS1 have been associated with autosomal-dominant Charcot-Marie-Tooth (CMT) neuropathy type C and a heterogenous group of autosomal recessive, multisystem diseases. We identified 12 individuals from 6 families with the recurrent homozygous missense variant c.1099C > T;p.(Arg367Trp) (NM{\_}003680.3) in YARS1. This variant causes a multisystem disorder with developmental delay, microcephaly, failure to thrive, short stature, muscular hypotonia, ataxia, brain anomalies, microcytic anemia, hepatomegaly, and hypothyroidism. In silico analyses show that the p.(Arg367Trp) does not affect the catalytic domain responsible of enzymatic coupling, but destabilizes the cytokine-like C-terminal domain. The phenotype associated with p.(Arg367Trp) is distinct from the other biallelic pathogenic variants that reside in different functional domains of TyrRS which all show some common, but also divergent clinical signs [(e.g., p.(Phe269Ser)-retinal anomalies, p.(Pro213Leu)/p.(Gly525Arg)-mild ID, p.(Pro167Thr)-high fatality)]. The diverse clinical spectrum of ARS1-associated disorders is related to mutations affecting the various non-canonical domains of ARS1, and impaired protein translation is likely not the exclusive disease-causing mechanism of YARS1- and ARS1-associated neurodevelopmental disorders. Key messages The missense variant p.(Arg367Trp) in YARS1 causes a distinct multisystem disorder. p.(Arg367Trp) affects a non-canonical domain with cytokine-like functions. Phenotypic heterogeneity associates with the different affected YARS1 domains. Impaired protein translation is likely not the exclusive mechanism of ARS1-associated disorders.},
author = {Averdunk, Luisa and Sticht, Heinrich and Surowy, Harald and Luedecke, Hermann-Josef and Koch-Hogrebe, Margarete and Alsaif, Hessa S. and Kahrizi, Kimia and Alzaidan, Hamad and Alawam, Bashayer S. and Tohary, Mohamed and Kraus, Cornelia and Endele, Sabine and Wadman, Erin and Kaplan, Julie D. and Efthymiou, Stephanie and Najmabadi, Hossein and Reis, André and Alkuraya, Fowzan S. and Wieczorek, Dagmar},
doi = {10.1007/s00109-021-02124-9},
faupublication = {yes},
journal = {Journal of Molecular Medicine},
note = {CRIS-Team WoS Importer:2021-10-01},
peerreviewed = {Yes},
title = {{The} recurrent missense mutation p.({Arg367Trp}) in {YARS1} causes a distinct neurodevelopmental phenotype},
year = {2021}
}
@article{faucris.281192599,
abstract = {TCF4 haploinsufficiency by deletions, truncating variants or loss-of-function missense variants within the DNA-binding and protein interacting bHLH domain causes Pitt-Hopkins syndrome (PTHS). This neurodevelopmental disorder (NDD) is characterized by severe intellectual disability (ID), epilepsy, hyperbreathing and a typical facial gestalt. Only few aberrations of the N-terminus of TCF4 were associated with milder or atypical phenotypes. By personal communication and searching databases we assembled six cases with the novel, recurrent, de novo missense variant c.1165C > T, p.(Arg389Cys) in TCF4. This variant was identified by diagnostic exome or panel sequencing and is located upstream of the bHLH domain. All six individuals presented with moderate to severe ID with language impairment. Microcephaly occurred in two individuals, epilepsy only in one, and no breathing anomalies or myopia were reported. Facial gestalt showed some aspects of PTHS but was rather non-specific in most individuals. Interestingly, the variant is located within the AD2 activation domain next to a highly conserved coactivator-recruitment motif and might alter interaction with coactivator proteins independently from the bHLH domain. Our findings of a recurrent missense variant outside the bHLH domain in six individuals with an ID phenotype overlapping with but not typical for PTHS delineate a novel genotype-phenotype correlation for TCF4-related NDDs.},
author = {Popp, Bernt and Bienvenu, Thierry and Giurgea, Irina and Metreau, Julia and Kraus, Cornelia and Reis, André and Fischer, Jan and Bralo, Maria Palomares and Tenorio-Castano, Jair and Lapunzina, Pablo and Almoguera, Berta and Lopez-Grondona, Fermina and Sticht, Heinrich and Zweier, Christiane},
doi = {10.1111/cge.14206},
faupublication = {yes},
journal = {Clinical Genetics},
note = {CRIS-Team WoS Importer:2022-09-02},
peerreviewed = {Yes},
title = {{The} recurrent {TCF4} missense variant p.({Arg389Cys}) causes a neurodevelopmental disorder overlapping with but not typical for {Pitt}-{Hopkins} syndrome},
year = {2022}
}
@article{faucris.224369767,
abstract = {The chronic pain syndrome inherited erythromelalgia (IEM) is attributed to mutations in the voltage-gated sodium channel (NaV) 1.7. Still, recent studies targeting NaV1.7 in clinical trials have provided conflicting results. Here, we differentiated induced pluripotent stem cells from IEM patients with the NaV1.7/I848T mutation into sensory nociceptors. Action potentials in these IEM nociceptors displayed a decreased firing threshold, an enhanced upstroke, and afterhyperpolarization, all of which may explain the increased pain experienced by patients. Subsequently, we investigated the voltage dependence of the tetrodotoxin-sensitive NaV activation in these human sensory neurons using a specific prepulse voltage protocol. The IEM mutation induced a hyperpolarizing shift of NaV activation, which leads to activation of NaV1.7 at more negative potentials. Our results indicate that NaV1.7 is not active during subthreshold depolarizations, but that its activity defines the action potential threshold and contributes significantly to the action potential upstroke. Thus, our model system with induced pluripotent stem cell-derived sensory neurons provides a new rationale for NaV1.7 function and promises to be valuable as a translational tool to profile and develop more efficacious clinical analgesics.},
author = {Meents, Jannis E. and Bressan, Elisangela and Sontag, Stephanie and Foerster, Alec and Hautvast, Petra and Rösseler, Corinna and Hampl, Martin and Schüler, Herdit and Goetzke, Roman and Le, Thi Kim Chi and Kleggetveit, Inge Petter and Le Cann, Kim and Kerth, Clara and Rush, Anthony M. and Rogers, Marc and Kohl, Zacharias and Schmelz, Martin and Wagner, Wolfgang and Jørum, Ellen and Namer, Barbara and Winner, Beate and Zenke, Martin and Lampert, Angelika},
doi = {10.1097/j.pain.0000000000001511},
faupublication = {yes},
journal = {Pain},
keywords = {Action potential firing; Erythromelalgia; Induced pluripotent stem cells; Inherited pain syndrome; iPS cells; Nociceptor; Pain; Patch-clamp; Voltage-gated sodium channel},
note = {CRIS-Team Scopus Importer:2019-08-13},
pages = {1327-1341},
peerreviewed = {Yes},
title = {{The} role of {Nav1}.7 in human nociceptors: {Insights} from human induced pluripotent stem cell-derived sensory neurons of erythromelalgia patients},
volume = {160},
year = {2019}
}
@article{faucris.108546064,
abstract = {The vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650) in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation. Notably, not a single parenthood of a homozygous c.657del5 carrier has been reported to date, while heterozygous carriers do reproduce but have an increased cancer risk. These observations seem to conflict with the considerable carrier frequency of c.657del5 of 0.5% to 1% as observed in different Slavic populations because deleterious mutations would be eliminated quite rapidly by purifying selection. Therefore, we propose that heterozygous c.657del5 carriers have increased reproductive success, i.e., that the mutation confers heterozygote advantage. In fact, in our cohort study of the reproductive history of 24 NBS pedigrees from the Czech Republic, we observed that female carriers gave birth to more children on average than female non-carriers, while no such reproductive differences were observed for males. We also estimate that c.657del5 likely occurred less than 300 generations ago, thus supporting the view that the original mutation predated the historic split and subsequent spread of the 'Slavic people'. We surmise that the higher fertility of female c.657del5 carriers reflects a lower miscarriage rate in these women, thereby reflecting the role of the NBN gene product, nibrin, in the repair of DNA double strand breaks and their processing in immune gene rearrangements, telomere maintenance, and meiotic recombination, akin to the previously described role of the DNA repair genes BRCA1 and BRCA2.},
author = {Seemanova, Eva and Varon, Raymonda and Vejvalka, Jan and Jarolim, Petr and Seeman, Pavel and Chrzanowska, Krystyna H. and Digweed, Martin and Resnick, Igor and Kremensky, Ivo and Saar, Kathrin and Hoffmann, Katrin and Dutrannoy, Veronique and Karbasiyan, Mohsen and Ghani, Mehdi and Baric, Ivo and Tekin, Mustafa and Kovacs, Peter and Krawczak, Michael and Reis, André and Sperling, Karl and Nothnagel, Michael},
doi = {10.1371/journal.pone.0167984},
faupublication = {yes},
journal = {PLoS ONE},
note = {EVALuna2:9351},
pages = {e0167984},
peerreviewed = {Yes},
title = {{The} {Slavic} {NBN} {Founder} {Mutation}: {A} {Role} for {Reproductive} {Fitness}?},
volume = {11},
year = {2016}
}
@incollection{faucris.240310893,
abstract = {Clinical decision support systems (CDSS) help to improve the diagnostics and treatment of rare diseases (RD). As one of four funded consortia of the Medical Informatics Initiative supported by the Federal Ministry of Education and Research (BMBF, Germany), MIRACUM develops a clinical decision support system (CDSS) for RD based on distributed data of ten university hospitals. The CDSS will be developed at the Rare Diseases Centres (RDC) of the MIRACUM consortium. Since it is essential to deliver decision support at the right time and place in the clinician's workflow, this study aimed to capture relevant information of the RDCs regarding patient admission and diagnostic process. Additionally, we investigated how patient documentation and digitalisation is performed at the centres. Therefore, we conducted a cross-sectional survey involving experts in the RDs domain to capture relevant information for the further development of a CDSS in RD. For each centre, one expert on RDs participated in the study (n=8). The survey identified several challenges regarding the reuse of patient data, e.g. the paper-based documentation of a patientâĂŹs medical history and coding of diagnoses using ICD-10. However, we noticed a relevant use of current software diagnosis support and a similarly performed diagnostic process in all RDC. Further studies are needed to get more detailed insights and to define specific requirements.},
author = {Schaaf, Jannik and Sedlmayr, Martin and Prokosch, Hans-Ulrich and Ganslandt, Thomas and Schade-Brittinger, Carmen and von Wagner, Michael and Kadioglu, Dennis and Schubert, Katharina and Lee-Kirsch, Min Ae and Kraemer, Bernhard K. and Winner, Beate and Mueller, Tobias and Schaefer, Juergen R. and Wagner, Thomas O.F. and Bruckner-Tuderman, Leena and Tuescher, Oliver and Boeker, Martin and Storf, Holger},
booktitle = {dHealth 2020 – Biomedical Informatics for Health and Care},
doi = {10.3233/SHTI200094},
editor = {Günter Schreier, Dieter Hayn, Alphons Eggerth},
faupublication = {yes},
keywords = {clinical decision support; quantitative analysis; rare diseases},
note = {CRIS-Team Scopus Importer:2020-07-10},
pages = {176-183},
peerreviewed = {unknown},
series = {Studies in Health Technology and Informatics},
title = {{The} {Status} {Quo} of {Rare} {Diseases} {Centres} for the {Development} of a {Clinical} {Decision} {Support} {System} - {A} {Cross}-{Sectional} {Study}},
volume = {271},
year = {2020}
}
@article{faucris.122892264,
abstract = {Adult neurogenesis mirrors the brain´s endogenous capacity to generate new neurons throughout life. In the subventricular zone/ olfactory bulb system adult neurogenesis is linked to physiological olfactory function and has been shown to be impaired in murine models of neuronal alpha-Synuclein overexpression. We analyzed the degree and temporo-spatial dynamics of adult olfactory bulb neurogenesis in transgenic mice expressing human wild-type alpha-Synuclein (WTS) under the murine Thy1 (mThy1) promoter, a model known to have a particularly high tg expression associated with impaired olfaction.Survival of newly generated neurons (NeuN-positive) in the olfactory bulb was unchanged in mThy1 transgenic animals. Due to decreased dopaminergic differentiation a reduction in new dopaminergic neurons within the olfactory bulb glomerular layer was present. This is in contrast to our previously published data on transgenic animals that express WTS under the control of the human platelet-derived growth factor ? (PDGF) promoter, that display a widespread decrease in survival of newly generated neurons in regions of adult neurogenesis, resulting in a much more pronounced neurogenesis deficit. Temporal and quantitative expression analysis using immunofluorescence co-localization analysis and Western blots revealed that in comparison to PDGF transgenic animals, in mThy1 transgenic animals WTS is expressed from later stages of neuronal maturation only but at significantly higher levels both in the olfactory bulb and cortex.The dissociation between higher absolute expression levels of alpha-Synuclein but less severe impact on adult olfactory neurogenesis in mThy1 transgenic mice highlights the importance of temporal expression characteristics of alpha-Synuclein on the maturation of newborn neurons.},
author = {Schreglmann, Sebastian R. and Regensburger, Martin and Rockenstein, Edward and Masliah, Eliezer and Xiang, Wei and Winkler, Jürgen and Winner, Beate},
doi = {10.1371/journal.pone.0126261},
faupublication = {yes},
journal = {PLoS ONE},
note = {EVALuna2:4712},
pages = {e0126261},
peerreviewed = {Yes},
title = {{The} temporal expression pattern of alpha-synuclein modulates olfactory neurogenesis in transgenic mice},
volume = {10},
year = {2015}
}
@article{faucris.204921130,
abstract = {Neuronal degeneration is a common mechanism of many neurological diseases including Parkinson's disease (PD), Alzheimer's disease (AD), and Multiple Sclerosis (MS). While AD and PD are classical neurodegenerative diseases, the primary pathology in MS is driven by autoimmune inflammation, attacking oligodendrocytes and thereby inducing neurodegeneration. In AD and PD, immune cells are also considered to play an important role in the disease progression. While the role of local central nervous system (CNS) innate immune cells is well described, a potential influence of adaptive immune cells in PD and AD is not yet fully understood.Here, we aim to summarize findings concerning adaptive immune cells in PD pathogenesis and compare them to AD and MS. In the first part, we focus on disease-specific alterations of lymphocytes in the circulating blood. Subsequently, we describe what is known about CNS-infiltrated lymphocytes and mechanisms of their infiltration. Finally, we summarize published data and try to understand the mechanisms of how lymphocytes contribute to neurodegeneration in PD, AD, and MS.Lymphocytes are critically involved in the pathogenesis of MS, and clarifying the role of lymphocytes in PD and AD pathogenesis might lead to an identification of a common signature of lymphocytes in neurodegeneration and thus pave the road towards novel treatment options.
},
author = {Sommer, Annika and Winner, Beate and Prots, Iryna},
doi = {10.1186/s13024-017-0222-8},
faupublication = {yes},
journal = {Molecular Neurodegeneration},
note = {EVALuna2:34020},
peerreviewed = {Yes},
title = {{The} {Trojan} horse - neuroinflammatory impact of {T} cells in neurodegenerative diseases},
volume = {12},
year = {2017}
}
@article{faucris.252913048,
abstract = {We report the clinical, structural, functional and genetic characterization of a 37-year-old Caucasian female, presenting as a sporadic case of complicated spastic paraplegia with thin corpus callosum (CC), cognitive impairment, amyotrophy of the hand muscles and a sensorimotor neuropathy and review the literature for spastic paraplegia with thin CC. Magnetic resonance imaging (MRI) examination revealed a thin CC with fronto-parietal cortical atrophy. 18Fluordesoxyglucose positron emission tomography (FDG-PET) showed reduced cortical and thalamic metabolism. By transcranial magnetic stimulation, we delineated a severe impairment of transcallosal inhibition. Sequence analysis did not reveal disease causing mutations in the genes SLC12A6 (Andermann), Spastin (SPG 4), BSCL2 (SPG 17) and Spartin (SPG 20). We reviewed the literature for HSP with thin CC and found 113 HSP patients with thin CC previously described (35 with linkage to chromosome 15q13-15). Thin CC and peripheral neuropathy often appear together in spastic paraplegia and might be indicative for combined degeneration mechanism of central and peripheral axons.},
author = {Winner, Beate and Winkler, Jürgen and Bogdahn, Ulrich and Hehr, Ute and et al.},
author_hint = {Winner, Gross, Uyanik, Schulte-Mattler, Lürding, Marienhagen, Bogdahn, Windpassinger, Hehr, Winkler},
doi = {10.1016/j.clineuro.2005.06.007},
faupublication = {no},
journal = {Clinical Neurology and Neurosurgery},
pages = {692-8},
peerreviewed = {Yes},
support_note = {Author relations incomplete. You may find additional data in field 'author{\_}hint'},
title = {{Thin} corpus callosum and amyotrophy in spastic paraplegia--case report and review of literature.},
volume = {108},
year = {2006}
}
@article{faucris.121820864,
abstract = {After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC) or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU) to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord) and unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement.},
author = {Franz, Steffen and Ciatipis, Mareva and Pfeifer, Kathrin and Kierdorf, Birthe and Sandner, Beatrice and Bogdahn, Ulrich and Blesch, Armin and Winner, Beate and Weidner, Norbert},
doi = {10.1371/journal.pone.0102896},
faupublication = {yes},
journal = {PLoS ONE},
note = {EVALuna2:26226},
pages = {e102896},
peerreviewed = {Yes},
title = {{Thoracic} rat spinal cord contusion injury induces remote spinal gliogenesis but not neurogenesis or gliogenesis in the brain},
volume = {9},
year = {2014}
}
@article{faucris.213410588,
abstract = {Mutations in SPG11 cause a complicated autosomal recessive form of hereditary spastic paraplegia (HSP). Mechanistically, there are indications for the dysregulation of the GSK3 beta/beta Cat signaling pathway in SPG11. In this study, we tested the therapeutic potential of the GSK3 beta inhibitor, tideglusib, to rescue neurodegeneration associated characteristics in an induced pluripotent stem cells (iPSCs) derived neuronal model from SPG11 patients and matched healthy controls as well as a CRISPR-Cas9 mediated SPG11 knock-out line and respective control. SPG11-iPSC derived cortical neurons, as well as the genome edited neurons exhibited shorter and less complex neurites than controls. Administration of tideglusib to these lines led to the rescue of neuritic impairments. Moreover, the treatment restored increased cell death and ameliorated the membranous inclusions in iPSC derived SPG11 neurons. Our results provide a first evidence for the rescue of neurite pathology in SPG11-HSP by tideglusib. The current lack of disease-modifying treatments for SPG11 and related types of complicated HSP renders tideglusib a candidate compound for future clinical application.},
author = {Pozner, Tatyana and Schray, Annika and Regensburger, Martin and Lie, Dieter Chichung and Schlötzer-Schrehardt, Ursula and Winkler, Jürgen and Turan, Sören and Winner, Beate},
doi = {10.3389/fnins.2018.00914},
faupublication = {yes},
journal = {Frontiers in Neuroscience},
keywords = {CRISPR knock-out; GSK3β inhibitor; SPG11; hereditary spastic paraplegia; induced pluripotent stem cell; neuronal culture; tideglusib},
note = {EVALuna2:35778},
pages = {914},
peerreviewed = {Yes},
title = {{Tideglusib} {Rescues} {Neurite} {Pathology} of {SPG11} {iPSC} {Derived} {Cortical} {Neurons}.},
volume = {12},
year = {2018}
}
@article{faucris.121230604,
abstract = {ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition-dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1(hi) effector CD8(+) T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8(+) T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1(hi) effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8(+) T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8(+) T cells.},
author = {Omilusik, Kyla D. and Best, J. Adam and Yu, Bingfei and Goossens, Steven and Weidemann, Alexander and Nguyen, Jessica V. and Seuntjens, Eve and Stryjewska, Agata and Zweier, Christiane and Roychoudhuri, Rahul and Gattinoni, Luca and Bird, Lynne M. and Higashi, Yujiro and Kondoh, Hisato and Huylebroeck, Danny and Haigh, Jody and Goldrath, Ananda W.},
doi = {10.1084/jem.20150194},
faupublication = {yes},
journal = {Journal of Experimental Medicine},
note = {EVALuna2:3800},
pages = {2027-39},
peerreviewed = {Yes},
title = {{Transcriptional} repressor {ZEB2} promotes terminal differentiation of {CD8}+ effector and memory {T} cell populations during infection},
volume = {212},
year = {2015}
}
@article{faucris.238798804,
abstract = {Development of oligodendrocytes and myelin formation in the vertebrate central nervous system is under control of several basic helix-loop-helix transcription factors such as Olig2, Ascl1, Hes5 and the Id proteins. The class I basic helix-loop-helix proteins Tcf3, Tcf4 and Tcf12 represent potential heterodimerization partners and functional modulators for all, but have not been investigated in oligodendrocytes so far. Using mouse mutants, organotypic slice and primary cell cultures we here show that Tcf4 is required in a cell-autonomous manner for proper terminal differentiation and myelination in vivo and ex vivo. Partial compensation is provided by the paralogous Tcf3, but not Tcf12. On the mechanistic level Tcf4 was identified as the preferred heterodimerization partner of the central regulator of oligodendrocyte development Olig2. Both genetic studies in the mouse as well as functional studies on enhancer regions of myelin genes confirmed the relevance of this physical interaction for oligodendrocyte differentiation. Considering that alterations in TCF4 are associated with syndromic and non-syndromic forms of intellectual disability, schizophrenia and autism in humans, our findings point to the possibility of an oligodendroglial contribution to these disorders.},
author = {Wedel, Miriam and Fröb, Franziska and Elsesser, Olga and Wittmann, Marie-Theres and Lie, Dieter Chichung and Reis, André and Wegner, Michael},
doi = {10.1093/nar/gkaa218},
faupublication = {yes},
journal = {Nucleic Acids Research},
note = {CRIS-Team Scopus Importer:2020-05-29},
pages = {4839-4857},
peerreviewed = {Yes},
title = {{Transcription} factor {Tcf4} is the preferred heterodimerization partner for {Olig2} in oligodendrocytes and required for differentiation},
volume = {48},
year = {2020}
}
@article{faucris.213354952,
abstract = {Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Transcriptome-pathology correlation identified casein kinase 1 epsilon (CSNK1E) mRNA as tightly correlated to levels of pTDP-43 in sALS patients. Enhanced crosslinking and immunoprecipitation in human sALS patient- and healthy control-derived frontal cortex, revealed that TDP-43 binds directly to and regulates the expression of CSNK1E mRNA. Additionally, we were able to show that pTDP-43 itself binds RNA. CK1E, the protein product of CSNK1E, in turn interacts with TDP-43 and promotes cytoplasmic accumulation of pTDP-43 in human stem-cell-derived MNs. Pathological TDP-43 phosphorylation is therefore, reciprocally regulated by CK1E activity and TDP-43 RNA binding. Our framework of transcriptome-pathology correlations identifies candidate genes with relevance to novel mechanisms of neurodegeneration.},
author = {Krach, Florian and Batra, Ranjan and Wheeler, Emily C. and Vu, Anthony Q. and Wang, Ruth and Hutt, Kasey and Rabin, Stuart J. and Baughn, Michael W. and Libby, Ryan T. and Diaz-Garcia, Sandra and Stauffer, Jennifer and Pirie, Elaine and Saberi, Shahram and Rodriguez, Maria and Madrigal, Assael A. and Kohl, Zacharias and Winner, Beate and Yeo, Gene W. and Ravits, John},
doi = {10.1007/s00401-018-1870-7},
faupublication = {yes},
journal = {Acta Neuropathologica},
note = {EVALuna2:35779},
pages = {405-423},
peerreviewed = {Yes},
title = {{Transcriptome}-pathology correlation identifies interplay between {TDP}-43 and the expression of its kinase {CK1E} in sporadic {ALS}},
volume = {136},
year = {2018}
}
@inproceedings{faucris.265787595,
address = {NEW YORK},
author = {Hüffmeier, Ulrike and Frey, Benjamin and Becker, Ina and Atreya, Imke and Berking, Carola and Moessner, R. and Wilsmann-Theis, D. and Uebe, Steffen and Kirchner, P. and Haskamp, Stefan},
booktitle = {JOURNAL OF INVESTIGATIVE DERMATOLOGY},
doi = {10.1016/j.jid.2021.08.235},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-11-05},
pages = {S188-S188},
peerreviewed = {unknown},
publisher = {ELSEVIER SCIENCE INC},
title = {{Transcriptomes} of {MPO}-deficient patients with generalized pustular psoriasis reveals expansion of {CD4}+cytotoxic {T} cells and an involvement of complement system and interferon pathways},
year = {2021}
}
@article{faucris.277563548,
abstract = {Generalized pustular psoriasis is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. Although variants in IL36RN and MPO have been shown to affect immune cells, a systematic analysis of neutrophils and PBMC subsets and their differential gene expression dependent on MPO genotypes was not performed yet. We assessed the transcriptomes of MPO-deficient patients using single-cell RNA sequencing of PBMCs and RNA sequencing of neutrophils in a stable disease state. Cell-type annotation by multimodal reference mapping of single-cell RNA-sequencing data was verified by flow cytometry of surface and intracellular markers; the proportions of CD4+ cytotoxic T lymphocytes and other CD4+ effector cells were increased in generalized pustular psoriasis, whereas the frequencies of naïve CD4+ T cells were significantly lower. The expression of FGFBP2 marking CD4+ cytotoxic T lymphocytes and CD8+ effector memory T cells was elevated in patients with generalized pustular psoriasis with disease-contributing variants compared with that in noncarriers (P = 0.0015). In neutrophils, differentially expressed genes were significantly enriched in genes of the classical complement activation pathway. Future studies assessing affected cell types and pathways will show their contribution to generalized pustular psoriasis's pathogenesis and indicate whether findings can be transferred to the acute epidermal situation and whether depletion or inactivation of CD4+ cytotoxic T lymphocytes may be a reasonable therapeutic approach.},
author = {Haskamp, Stefan and Frey, Benjamin and Becker, Ina and Schulz-Kuhnt, Anja and Atreya, Imke and Berking, Carola and Pauli, David and Ekici, Arif Bülent and Berges, Johannes and Mößner, Rotraut and Wilsmann-Theis, Dagmar and Sticherling, Michael and Uebe, Steffen and Kirchner, Philipp and Hüffmeier, Ulrike},
doi = {10.1016/j.jid.2021.12.021},
faupublication = {yes},
journal = {Journal of Investigative Dermatology},
note = {CRIS-Team Scopus Importer:2022-07-08},
peerreviewed = {Yes},
title = {{Transcriptomes} of {MPO}-{Deficient} {Patients} with {Generalized} {Pustular} {Psoriasis} {Reveals} {Expansion} of {CD4}+ {Cytotoxic} {T} {Cells} and an {Involvement} of the {Complement} {System}},
year = {2022}
}
@article{faucris.231306897,
abstract = {Background Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract associated with abdominal pain and diarrhea. Pain caused by Crohn's disease likely involves neurogenic inflammation which seems to involve the ion channel transient receptor potential ankyrin 1 (TRPA1). Since the promoter methylation of TRPA1 was shown to influence pain sensitivity, we asked if the expression of TRPA1 is dysregulated in patients suffering from Crohn's disease. The methylation rates of CpG dinucleotides in the TRPA1 promoter region were determined from DNA derived from whole blood samples of Crohn patients and healthy participants. Quantitative sensory testing was used to examine pain sensitivities. Results Pressure pain thresholds were lower in Crohn patients as compared to healthy participants, and they were also lower in females than in males. They correlated inversely with the methylation rate at the CpG - 628 site of the TRPA1 promoter. This effect was more pronounced in female compared to male Crohn patients. Similar results were found for mechanical pain thresholds. Furthermore, age-dependent effects were detected. Whereas the CpG - 628 methylation rate declined with age in healthy participants, the methylation rate in Crohn patients increased. Pressure pain thresholds increased with age in both cohorts. Conclusions The TRPA1 promoter methylation appears to be dysregulated in patients suffering from Crohn's disease, and this effect is most obvious when taking gender and age into account. As TRPA1 is regarded to be involved in pain caused by neurogenic inflammation, its aberrant expression may contribute to typical symptoms of Crohn's disease.},
author = {Gombert, Sara and Rhein, Mathias and Winterpacht, Andreas and Münster, Tino and Hillemacher, Thomas and Leffler, Andreas and Frieling, Helge},
doi = {10.1186/s13148-019-0796-9},
faupublication = {yes},
journal = {Clinical Epigenetics},
note = {CRIS-Team WoS Importer:2020-01-10},
peerreviewed = {Yes},
title = {{Transient} receptor potential ankyrin 1 promoter methylation and peripheral pain sensitivity in {Crohn}'s disease},
volume = {12},
year = {2019}
}
@article{faucris.281420596,
abstract = {Alpha synuclein (aSyn) and its aggregation are crucial for the neurodegeneration of Parkinson's disease (PD). aSyn was initially described in the nucleus and presynaptic nerve terminals. However, the biology of nuclear aSyn and the link of aSyn between subcellular compartments are less understood. Current knowledge suggests the existence of various aSyn species with distinct structural and biochemical properties. Here, we identified a C-terminal-targeting aSyn antibody (Nu-aSyn-C), which has a high immunoaffinity towards aSyn in the nucleus. Comparing the Nu-aSyn-C antibody to aSyn antibodies developed against phosphorylated or aggregated forms, we observed that nuclear aSyn differs from cytosolic aSyn by an increased phosphorylation and assembly level in proliferating cells. Employing Nu-aSyn-C, we characterized aSyn distribution during neuronal differentiation in midbrain dopaminergic neurons (mDANs) derived from human-induced pluripotent stem cells (hiPSCs) and Lund human mesencephalic cells, and in primary rat hippocampal neurons. We detected a specific translocation pattern of aSyn during neuronal differentiation from the nucleus to the soma and finally to neuronal processes. Interestingly, a remarkable shift of Nu-aSyn-C-positive species towards neurites was detected in hiPSC mDANs from a PD patient carrying aSyn gene duplication. Together, our results reveal distinct nuclear and cytosolic aSyn species that redistribute during neuronal differentiation-a process that is altered in PD-derived neurons.},
author = {Pieger, Katharina and Schmitt, Verena and Gauer, Carina and Gießl, Nadja and Prots, Iryna and Winner, Beate and Winkler, Jürgen and Brandstätter, Johann Helmut and Xiang, Wei},
doi = {10.3390/biom12081108},
faupublication = {yes},
journal = {Biomolecules},
note = {CRIS-Team WoS Importer:2022-09-09},
peerreviewed = {Yes},
title = {{Translocation} of {Distinct} {Alpha} {Synuclein} {Species} from the {Nucleus} to {Neuronal} {Processes} during {Neuronal} {Differentiation}},
volume = {12},
year = {2022}
}
@article{faucris.216825831,
abstract = {Two percent of patients with Wilms tumors have a positive family history. In many of these cases the genetic cause remains unresolved. By applying germline exome sequencing in two families with two affected individuals with Wilms tumors, we identified truncating mutations in TRIM28. Subsequent mutational screening of germline and tumor DNA of 269 children affected by Wilms tumor was performed, and revealed seven additional individuals with germline truncating mutations, and one individual with a somatic truncating mutation in TRIM28. TRIM28 encodes a complex scaffold protein involved in many different processes, including gene silencing, DNA repair and maintenance of genomic integrity. Expression studies on mRNA and protein level showed reduction of TRIM28, confirming a loss-of-function effect of the mutations identified. The tumors showed an epithelial-type histology that stained negative for TRIM28 by immunohistochemistry. The tumors were bilateral in six patients, and 10/11 tumors are accompanied by perilobar nephrogenic rests. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development. Additionally, the tumors showed very few mutations in known Wilms tumor driver genes, suggesting that loss of TRIM28 is the main driver of tumorigenesis. In conclusion, we identified heterozygous germline truncating mutations in TRIM28 in 11 children with mainly epithelial-type Wilms tumors, which become homozygous in tumor tissue. These data establish TRIM28 as a novel Wilms tumor predisposition gene, acting as a tumor suppressor gene by LOH.},
author = {Diets, Illja J. and Hoyer, Juliane and Ekici, Arif Bülent and Popp, Bernt and Hoogerbrugge, Nicoline and van Reijmersdal, Simon V. and Bhaskaran, Rajith and Hadjihannas, Michel and Vasileiou, Georgia and Thiel, Christian and Seven, Didem and Uebe, Steffen and Ilencikova, Denisa and Waanders, Esmé and Mavinkurve-Groothuis, Annelies M.C. and Roeleveld, Nel and de Krijger, Ronald R. and Wegert, Jenny and Graf, Norbert and Vokuhl, Christian and Agaimy, Abbas and Gessler, Manfred and Reis, André and Kuiper, Roland P. and Jongmans, Marjolijn C.J. and Metzler, Markus},
doi = {10.1002/ijc.32167},
faupublication = {yes},
journal = {International Journal of Cancer},
keywords = {genetic predisposition; haploinsufficiency; TRIM28; Wilms tumor},
note = {CRIS-Team Scopus Importer:2019-05-02},
peerreviewed = {Yes},
title = {{TRIM28} haploinsufficiency predisposes to {Wilms} tumor},
year = {2019}
}
@article{faucris.313207863,
author = {Naschberger, Elisabeth and Fuchs, Maximilian and Dickel, Nicholas and Kunz, Meik and Popp, Bernt and Anchang, Charles Gwellem and Demmler, Richard and Lyu, Yanmin and Uebe, Steffen and Ekici, Arif Bülent and Geppert, Carol-Immanuel and Hartmann, Arndt and Flierl, Christian and Petter, Katja and Gass, Tobias and Völkl, Simon and Scharl, Michael and Ramming, Andreas and Günther, Claudia and Merkel, Susanne and Schellerer, Vera and Stürzl, Michael},
doi = {10.1002/cac2.12489},
faupublication = {yes},
journal = {Cancer Communications},
note = {CRIS-Team Scopus Importer:2023-10-27},
peerreviewed = {Yes},
title = {{Tumor} microenvironment-dependent epigenetic imprinting in the vasculature predicts colon cancer outcome},
year = {2023}
}
@inproceedings{faucris.208217602,
author = {Clahsen, Thomas and Regenfuss, Birgit and Büttner, Christian and Gabriel, Tim and Bock, Felix and Reis, André and Cursiefen, Claus},
faupublication = {yes},
note = {EVALuna2:34828},
peerreviewed = {Yes},
title = {{Tyrosinase} downregulates {Fibromodulin}- induced lymphangiogenesis},
volume = {59},
year = {2018}
}
@inproceedings{faucris.230857842,
author = {Clahsen, Thomas and Büttner, Christian and Regenfuss, Birgit and Gabriel, Tim and Bock, Felix and Reis, André and Cursiefen, Claus},
faupublication = {yes},
note = {EVALuna2:206970},
peerreviewed = {Yes},
title = {{Tyrosinase} is a novel endogenous inhibitor of lymphangiogenesis},
volume = {60},
year = {2019}
}
@article{faucris.208221212,
abstract = {Lymphangiogenesis is critically involved in tissue fluid balance, graft rejection, and tumor metastasis. Endogenous regulation of lymphangiogenesis is poorly understood. Here we use the lymphatic vessel architecture at the limbal border of the normally avascular cornea, a quantitative trait under strong genetic influence, as a model system to identify new candidate genes regulating lymphangiogenesis. Comparing low-lymphangiogenic BALB/cN versus high-lymphangiogenic C57BL/6N mice, we performed quantitative trait loci analysis of five phenotypes in a large BALB/cN x C57BL/6N intercross (n=795) and identified three to eight genome-wide significant loci, the strongest on chromosome 7 containing Tyrosinase (Tyr). Tyrosinase-negative mice showed significantly increased limbal lymphvascularized areas, a higher number of lymphatic vessel endpoints, and branching points and increased inflammation-induced lymphangiogenesis. These findings confirm that tyrosinase is a novel lymphangiogenesis regulator in developmental and inflammatory lymphangiogenesis. Our findings link melanin synthesis with lymphangiogenesis and open new treatment options in lymphangiogenesis-related diseases.},
author = {Büttner, Christian and Clahsen, Thomas and Regenfuss, Birgit and Dreisow, Marie Luise and Steiber, Zita and Bock, Felix and Reis, André and Cursiefen, Claus},
doi = {10.1016/j.ajpath.2018.10.014},
faupublication = {yes},
journal = {American Journal of Pathology},
note = {EVALuna2:34844},
peerreviewed = {Yes},
title = {{Tyrosinase} is a novel endogenous regulator of developmental and inflammatory lymphangiogenesis},
year = {2018}
}
@inproceedings{faucris.282436987,
address = {ROCKVILLE},
author = {Clahsen, Thomas and Hatami, Niloofar and Büttner, Christian and Reis, André and Cursiefen, Claus},
booktitle = {INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2022-09-30},
peerreviewed = {unknown},
publisher = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
title = {{Tyrosinase} reduces expression of vascular endothelial growth factors and improves corneal graft survival},
year = {2022}
}
@inproceedings{faucris.248094548,
address = {LONDON},
author = {Kraus, Cornelia and Mammadova, Dilbar and Leis, T. and Ekici, Arif Bülent and Thiel, C. and Reis, André and Trollmann, Regina},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {325-325},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Unexpected} phenotypic variability in a family with epilepsy explained by independent segregation of biparental {CACNA1A} loss-of-function variants},
year = {2020}
}
@article{faucris.243600320,
abstract = {Senescence was recently linked to neurodegeneration and astrocytes are one of the major cell types to turn senescent under neurodegenerative conditions. Senescent astrocytes were detected in Parkinson's disease (PD) patients' brains besides reactive astrocytes, yet the difference between senescent and reactive astrocytes is unclear. We aimed to characterize senescent astrocytes in comparison to reactive astrocytes and investigate differences and similarities. In a cell culture model of human fetal astrocytes, we determined a unique senescent transcriptome distinct from reactive astrocytes, which comprises dysregulated pathways. Both, senescent and reactive human astrocytes activated a proinflammatory pattern. Astrocyte senescence was at least partially depending on active mechanistic-target-of-rapamycin (mTOR) and DNA-damage response signaling, both drivers of senescence. To further investigate how PD and senescence connect to each other, we asked if a PD-linked environmental factor induces senescence and if senescence impairs midbrain neurons. We could show that the PD-linked pesticide rotenone causes astrocyte senescence. We further delineate, that the senescent secretome exaggerates rotenone-induced neurodegeneration in midbrain neurons differentiated from human induced pluripotent stem cells (hiPSC) of PD patients with alpha-synuclein gene (SNCA) locus duplication.},
author = {Simmnacher, Katrin and Krach, Florian and Schneider, Yanni and Alecu, Julian E. and Mautner, Lena and Klein, Paulina and Roybon, Laurent and Prots, Iryna and Xiang, Wei and Winner, Beate},
doi = {10.1016/j.expneurol.2020.113466},
faupublication = {yes},
journal = {Experimental Neurology},
keywords = {Alpha synuclein; Astrocyte neuron interplay; iPSC derived neurons; Parkinson's disease; Reactive astrocyte; Rotenone; Senescence},
note = {CRIS-Team Scopus Importer:2020-10-09},
peerreviewed = {Yes},
title = {{Unique} signatures of stress-induced senescent human astrocytes},
volume = {334},
year = {2020}
}
@inproceedings{faucris.248111899,
address = {LONDON},
author = {Asadollahi, R. and Boonsawat, P. and Popp, B. and Torti, E. and Bader, I. and Vitobello, A. and Moutton, S. and Pinson, L. and Lambert, L. and Thuresson, A. C. and Sobol, M. and Zander, C. Soussi and Platzer, K. and Strehlow, V. and Hornemann, F. and Zacher, P. and Mau-Them, F. Tran and Bruel, A. L. and Hajianpour, M. J. and Kovacs-Nagy, R. and Lay-Son, G. and Amlie-Wolf, L. and Kaplan, J. and Chassevent, A. and Smith-Hicks, C. and Slavotinek, A. and Kukolich, M. K. and Nugent, K. and Roeder, E. and Zarate, Y. A. and Toshiyuki, Y. and Jackel-Cram, C. and Maystadt, I. and Mehta, S. G. and Briggs, T. A. and Chandler, K. and Van Haeringen, A. and Kraus, Cornelia and Zweier, Christiane and Reis, André and Rauch, A.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {350-351},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Updated} insight into the mutational and phenotypic spectrum of {MED13L}-related intellectual disability},
year = {2020}
}
@article{faucris.121100364,
abstract = {The molecular events responsible for obstruction of aqueous humor outflow and the loss of retinal ganglion cells in glaucoma, one of the main causes of blindness worldwide, remain poorly understood. We identified a synonymous variant, c.765C>T (Thr255Thr), in ankyrin repeats and suppressor of cytokine signaling box-containing protein 10 (ASB10) in a large family with primary open angle glaucoma (POAG) mapping to the GLC1F locus. This variant affects an exon splice enhancer site and alters mRNA splicing in lymphoblasts of affected family members. Systematic sequence analysis in two POAG patient groups (195 US and 977 German) and their respective controls (85 and 376) lead to the identification of 26 amino acid changes in 70 patients (70 of 1172; 6.0%) compared with 9 in 13 controls (13 of 461; 2.8%; P = 0.008). Molecular modeling suggests that these missense variants change ASB10 net charge or destabilize ankyrin repeats. ASB10 mRNA and protein were found to be strongly expressed in trabecular meshwork, retinal ganglion cells and ciliary body. Silencing of ASB10 transcripts in perfused anterior segment organ culture reduced outflow facility by ~50% compared with control-infected anterior segments (P = 0.02). In conclusion, genetic and molecular analyses provide evidence for ASB10 as a glaucoma-causing gene.},
author = {Pasutto, Francesca and Keller, Kate E. and Weisschuh, Nicole and Sticht, Heinrich and Samples, John R. and Yang, Yong-Feng and Zenkel, Matthias and Schlötzer-Schrehardt, Ursula and Mardin, Christian Y. and Frezzotti, Paolo and Edmunds, Beth and Kramer, Patricia L. and Gramer, Eugen and Reis, André and Acott, Ted S. and Wirtz, Mary K.},
doi = {10.1093/hmg/ddr572},
faupublication = {yes},
journal = {Human Molecular Genetics},
note = {EVALuna2:9125},
pages = {1336-49},
peerreviewed = {Yes},
title = {{Variants} in {ASB10} are associated with open-angle glaucoma},
volume = {21},
year = {2012}
}
@article{faucris.237909700,
abstract = {We describe six persons from three families with three homozygous protein truncating variants in PUS7: c.89{\_}90del (p.Thr30Lysfs∗20), c.1348C>T (p.Arg450∗), and a deletion of the penultimate exon 15. All these individuals have intellectual disability with speech delay, short stature, microcephaly, and aggressive behavior. PUS7 encodes the RNA-independent pseudouridylate synthase 7. Pseudouridylation is the most abundant post-transcriptional modification in RNA, which is primarily thought to stabilize secondary structures of RNA. We show that the disease-related variants lead to abolishment of PUS7 activity on both tRNA and mRNA substrates. Moreover, pus7 knockout in Drosophila melanogaster results in a number of behavioral defects, including increased activity, disorientation, and aggressiveness supporting that neurological defects are caused by PUS7 variants. Our findings demonstrate that RNA pseudouridylation by PUS7 is essential for proper neuronal development and function.},
author = {De Brouwer, Arjan P. M. and Abou Jamra, Rami and Koertel, Nadine and Soyris, Clara and Polla, Daniel L. and Safra, Modi and Zisso, Avia and Powell, Christopher A. and Rebelo-Guiomar, Pedro and Dinges, Nadja and Morin, Violeta and Stock, Michael and Hussain, Mureed and Shahzad, Mohsin and Riazuddin, Saima and Ahmed, Zubair M. and Pfundt, Rolph and Schwarz, Franziska and De Boer, Lonneke and Reis, André and Grozeva, Detilina and Raymond, F. Lucy and Riazuddin, Sheikh and Koolen, David A. and Minczuk, Michal and Roignant, Jean-Yves and Van Bokhoven, Hans and Schwartz, Schraga},
doi = {10.1016/j.ajhg.2018.10.026},
faupublication = {yes},
journal = {American Journal of Human Genetics},
note = {EVALuna2:215758},
pages = {1045-1052},
peerreviewed = {Yes},
title = {{Variants} in {PUS7} {Cause} {Intellectual} {Disability} with {Speech} {Delay}, {Microcephaly}, {Short} {Stature}, and {Aggressive} {Behavior}},
volume = {103},
year = {2018}
}
@article{faucris.241752189,
abstract = {RNA polymerase II interacts with various other complexes and factors to ensure correct initiation, elongation, and termination of mRNA transcription. One of these proteins is SR-related CTD-associated factor 4 (SCAF4), which is important for correct usage of polyA sites for mRNA termination. Using exome sequencing and international matchmaking, we identified nine likely pathogenic germline variants in SCAF4 including two splice-site and seven truncating variants, all residing in the N-terminal two thirds of the protein. Eight of these variants occurred de novo, and one was inherited. Affected individuals demonstrated a variable neurodevelopmental disorder characterized by mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies. Paired-end RNA sequencing on blood lymphocytes of SCAF4-deficient individuals revealed a broad deregulation of more than 9,000 genes and significant differential splicing of more than 2,900 genes, indicating an important role of SCAF4 in mRNA processing. Knockdown of the SCAF4 ortholog CG4266 in the model organism Drosophila melanogaster resulted in impaired locomotor function, learning, and short-term memory. Furthermore, we observed an increased number of active zones in larval neuromuscular junctions, representing large glutamatergic synapses. These observations indicate a role of CG4266 in nervous system development and function and support the implication of SCAF4 in neurodevelopmental phenotypes. In summary, our data show that heterozygous, likely gene-disrupting variants in SCAF4 are causative for a variable neurodevelopmental disorder associated with impaired mRNA processing.},
author = {Fliedner, Anna and Kirchner, Philipp and Wiesener, Antje and van de Beek, Irma and Waisfisz, Quinten and van Haelst, Mieke and Scott, Daryl A. and Lalani, Seema R. and Rosenfeld, Jill A. and Azamian, Mahshid S. and Xia, Fan and Dutra-Clarke, Marina and Martinez-Agosto, Julian A. and Lee, Hane and Nelson, Stanley F. and Grody, Wayne W. and Deignan, Joshua L. and Kang, Sung Hae and Arboleda, Valerie A. and Senaratne, T. Niroshi and Dorrani, Naghmeh and Dutra-Clarke, Marina S. and Kianmahd, Jessica and Hinkamp, Franceska L. and Neustadt, Ahna M. and Fogel, Brent L. and Quintero-Rivera, Fabiola and Noh, Grace J. and Lippa, Natalie and Alkelai, Anna and Aggarwal, Vimla and Agre, Katherine E. and Gavrilova, Ralitza and Mirzaa, Ghayda M. and Straussberg, Rachel and Cohen, Rony and Horist, Brooke and Krishnamurthy, Vidya and McWalter, Kirsty and Juusola, Jane and Davis-Keppen, Laura and Ohden, Lisa and van Slegtenhorst, Marjon and de Man, Stella A. and Ekici, Arif Bülent and Gregor, Anne and van de Laar, Ingrid and Zweier, Christiane},
doi = {10.1016/j.ajhg.2020.06.019},
faupublication = {yes},
journal = {American Journal of Human Genetics},
keywords = {epilepsy; intellectual disability; mRNA processing; neurodevelopmental disorder; SCAF4; seizures},
note = {CRIS-Team Scopus Importer:2020-08-21},
peerreviewed = {Yes},
title = {{Variants} in {SCAF4} {Cause} a {Neurodevelopmental} {Disorder} and {Are} {Associated} with {Impaired} {mRNA} {Processing}},
year = {2020}
}
@article{faucris.314301121,
abstract = {VEXAS syndrome is a recently identified autoinflammatory systemic disease caused by an acquired somatic mutation of the X-linked UBA1 gene, the key enzyme of the first step of ubiquitylation. The acronym VEXAS stands for the characteristics Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic. The disease occurs in advanced adulthood preferentially in men and is characterized by hematological, rheumatological and dermatological symptoms. The latter include neutrophil-rich lesions reminiscent of Sweet's syndrome, erythema nodosum- and panniculitis-like skin manifestations and recurrent polychondritis of the nose and auricles. The presence of cytoplasmic vacuoles in myeloid and erythroid precursors in the bone marrow is characteristic. In up to half of the cases, VEXAS syndrome is associated with myelodysplastic syndrome. Dermatologists should be familiar with the clinical picture, as skin symptoms are often the first indicator of the disease. Molecular diagnostics are essential for confirming the diagnosis and risk stratification of affected patients. In this minireview we provide an overview of the pathophysiology, diagnosis and therapy of VEXAS syndrome and illustrate its clinical picture with two own cases.},
author = {Baur, Vera and Stoevesandt, Johanna and Hueber, Axel and Hüffmeier, Ulrike and Kneitz, Hermann and Morbach, Henner and Schultz, Erwin and Goebeler, Matthias},
doi = {10.1111/ddg.15227},
faupublication = {yes},
journal = {Journal der Deutschen Dermatologischen Gesellschaft},
note = {CRIS-Team Scopus Importer:2023-11-24},
peerreviewed = {Yes},
title = {{VEXAS}-{Syndrome}, a newly described autoinflammatory systemic disease with dermatologic manifestations},
year = {2023}
}
@article{faucris.107295584,
abstract = {We report the identification of a novel mutation in the fork-head box C1 (FOXC1) gene which occurred de novo in an Italian patient with unrecognized Axenfeld-Rieger syndrome. He was previously diagnosed as having late recognized primary congenital glaucoma at the age of 14 years and was subsequently subjected to multiple surgical interventions due to uncontrolled intraocular pressure and progressive visual field loss. After exclusion of mutations in CYP1B1 and MYOC, trio-whole-exome sequencing revealed de novo in frame deletion in the coding region of the FOXC1 gene (c.407{\_}409delGTC, p.V137del) leading to a deletion of the evolutionary conserved amino acid Valine at position 137 of the protein. Molecular modeling predicted that Val137 deletion impairs FOXC1 DNA-binding capacity and transcriptional activation. Since loss-of-function mutations in FOXC1 are associated with Axenfeld-Rieger syndrome, the genetic findings in combination with re-evaluation of the patient's clinical data resulted in a corrected diagnosis of Axenfeld-Rieger syndrome with developmental glaucoma. We therefore suggest that in addition to CYP1B1 and MYOC, FOXC1 should be included in the genetic analysis of cases with unclear glaucomatous phenotypes to ensure proper diagnosis, adequate treatment and appropriate genetic counseling.},
author = {Pasutto, F. and Mauri, L. and Popp, Bernt and Sticht, Heinrich and Ekici, Arif Bülent and Piozzi, E. and Bonfante, A. and Penco, Silvana and Schlötzer-Schrehardt, Ursula and Reis, André},
doi = {10.1016/j.gene.2015.05.015},
faupublication = {yes},
journal = {Gene},
note = {EVALuna2:9257},
pages = {76-80},
peerreviewed = {Yes},
title = {{Whole} exome sequencing reveals a novel de novo {FOXC1} mutation in a patient with unrecognized {Axenfeld}-{Rieger} syndrome and glaucoma},
volume = {568},
year = {2015}
}
@article{faucris.120723504,
abstract = {The mechanisms that coordinate and balance a complex network of opposing regulators to control Schwann cell (SC) differentiation remain elusive. Here we demonstrate that zinc-finger E-box-binding homeobox 2 (Zeb2, also called Sip1) transcription factor is a critical intrinsic timer that controls the onset of SC differentiation by recruiting histone deacetylases HDAC 1 and 2 (HDAC1/2) and nucleosome remodeling and deacetylase complex (NuRD) co-repressor complexes in mice. Zeb2 deletion arrests SCs at an undifferentiated state during peripheral nerve development and inhibits remyelination after injury. Zeb2 antagonizes inhibitory effectors including Notch and Sox2. Importantly, genome-wide transcriptome analysis reveals a Zeb2 target gene encoding the Notch effector Hey2 as a potent inhibitor for Schwann cell differentiation. Strikingly, a genetic Zeb2 variant associated with Mowat-Wilson syndrome disrupts the interaction with HDAC1/2-NuRD and abolishes Zeb2 activity for SC differentiation. Therefore, Zeb2 controls SC maturation by recruiting HDAC1/2-NuRD complexes and inhibiting a Notch-Hey2 signaling axis, pointing to the critical role of HDAC1/2-NuRD activity in peripheral neuropathies caused by ZEB2 mutations.},
author = {Wu, Lai Man Natalie and Wang, Jincheng and Conidi, Andrea and Zhao, Chuntao and Wang, Haibo and Ford, Zachary and Zhang, Liguo and Zweier, Christiane and Ayee, Brian G. and Maurel, Patrice and Zwijsen, An and Chan, Jonah R. and Jankowski, Michael P. and Huylebroeck, Danny and Lu, Q. Richard},
doi = {10.1038/nn.4322},
faupublication = {yes},
journal = {Nature Neuroscience},
note = {EVALuna2:9316},
pages = {1060-72},
peerreviewed = {Yes},
title = {{Zeb2} recruits {HDAC}-{NuRD} to inhibit {Notch} and controls {Schwann} cell differentiation and remyelination},
volume = {19},
year = {2016}
}
@article{faucris.262175355,
abstract = {ZMYND11 is the critical gene in chromosome 10p15.3 microdeletion syndrome, a syndromic cause of intellectual disability. The phenotype of ZMYND11 variants has recently been extended to autism and seizures. We expand on the epilepsy phenotype of 20 individuals with pathogenic variants in ZMYND11. We obtained clinical descriptions of 16 new and nine published individuals, plus detailed case history of two children. New individuals were identified through GeneMatcher, ClinVar and the European Network for Therapies in Rare Epilepsy (NETRE). Genetic evaluation was performed using gene panels or exome sequencing; variants were classified using American College of Medical Genetics (ACMG) criteria. Individuals with ZMYND11 associated epilepsy fell into three groups: (i) atypical benign partial epilepsy or idiopathic focal epilepsy (n = 8); (ii) generalised epilepsies/infantile epileptic encephalopathy (n = 4); (iii) unclassified (n = 8). Seizure prognosis ranged from spontaneous remission to drug resistant. Neurodevelopmental deficits were invariable. Dysmorphic features were variable. Variants were distributed across the gene and mostly de novo with no precise genotype–phenotype correlation. ZMYND11 is one of a small group of chromatin reader genes associated in the pathogenesis of epilepsy, and specifically ABPE. More detailed epilepsy descriptions of larger cohorts and functional studies might reveal genotype–phenotype correlation. The epileptogenic mechanism may be linked to interaction with histone H3.3.},
author = {Oates, Stephanie and Absoud, Michael and Goyal, Sushma and Bayley, Sophie and Baulcomb, Jennifer and Sims, Annemarie and Riddett, Amy and Allis, Katrina and Brasch-Andersen, Charlotte and Balasubramanian, Meena and Bai, Renkui and Callewaert, Bert and Hüffmeier, Ulrike and Le Duc, Diana and Radtke, Maximilian and Korff, Christian and Kennedy, Joanna and Low, Karen and Moller, Rikke S. and Nielsen, Jens Erik Klint and Popp, Bernt and Quteineh, Lina and Ronde, Gitte and Schoenewolf-Greulich, Bitten and Shillington, Amelle and Taylor, Matthew R. G. and Todd, Emily and Torring, Pernille M. and Tuemer, Zeynep and Vasileiou, Georgia and Yates, T. Michael and Zweier, Christiane and Rosch, Richard and Basson, M. Albert and Pal, Deb K.},
doi = {10.1111/cge.14023},
faupublication = {yes},
journal = {Clinical Genetics},
keywords = {antiepileptic drug; autism; bromodomain; comorbidity; EEG; epigenetic; histone H3.3; seizure},
note = {CRIS-Team Scopus Importer:2021-07-30},
peerreviewed = {Yes},
title = {{ZMYND11} variants are a novel cause of centrotemporal and generalised epilepsies with neurodevelopmental disorder},
year = {2021}
}
@article{faucris.212621391,
abstract = {Human induced pluripotent stem cells (hiPSCs) are an important tool for research and regenerative medicine, but their efficient cryopreservation remains a major challenge. The current gold standard is slow-rate freezing of dissociated colonies in suspension, but low recovery rates limit immediate post-thawing applicability. We tested whether ultrafast cooling by adherent vitrification improves post-thawing survival in a selection of hiPSCs and small molecule neural precursor cells (smNPCs) from Parkinson's disease and controls. In a dual-center study, we compared the results by immunocytochemistry (ICC), fluorescence-activated cell sorting analysis, and RNA-sequencing (RNA-seq). Adherent vitrification was achieved in the so-called TWIST substrate, a device combining cultivation, vitrification, storage, and post-thawing cultivation. Adherent vitrification resulted in preserved confluency and significantly higher cell numbers, and viability at day 1 after thawing, while results were not significantly different at day 4 after thawing. RNA-seq and ICC of hiPSCs revealed no change in gene expression and pluripotency markers, indicating that physical damage of slow-rate freezing disrupts cellular membranes. Scanning electron microscopy showed preserved colony integrity by adherent vitrification. Experiments using smNPCs demonstrated that adherent vitrification is also applicable to neural derivatives of hiPSCs. Our data suggest that, compared to the state-of-the-art slow-rate freezing in suspension, adherent vitrification is an improved cryopreservation technique for hiPSCs and derivatives. Stem Cells Translational Medicine 2019;8:247&259.},
author = {Kaindl, Johanna and Meiser, Ina and Majer, Julia and Sommer, Annika and Krach, Florian and Katsen-Globa, Alisa and Winkler, Jürgen and Zimmermann, Heiko and Neubauer, Julia C. and Winner, Beate},
doi = {10.1002/sctm.18-0121},
faupublication = {yes},
journal = {Stem Cells Translational Medicine},
note = {EVALuna2:36383},
pages = {247-259},
peerreviewed = {Yes},
title = {{Zooming} in on {Cryopreservation} of {hiPSCs} and {Neural} {Derivatives}: {A} {Dual}-{Center} {Study} {Using} {Adherent} {Vitrification}},
volume = {8},
year = {2019}
}
@article{faucris.252913591,
abstract = {Multiple system atrophy (MSA), an atypical parkinsonian disorder, is characterized by α-synuclein (α-syn(+)) cytoplasmatic inclusions in mature oligodendrocytes. Oligodendrocyte progenitor cells (OPCs) represent a distinct cell population with the potential to replace dysfunctional oligodendrocytes. However, the role of OPCs in MSA and their potential to replace mature oligodendrocytes is still unclear. A postmortem analysis in MSA patients revealed α-syn within OPCs and an increased number of striatal OPCs. In an MSA mouse model, an age-dependent increase of dividing OPCs within the striatum and the cortex was detected. Despite of myelin loss, there was no reduction of mature oligodendrocytes in the corpus callosum or the striatum. Dissecting the underlying molecular mechanisms an oligodendroglial cell line expressing human α-syn revealed that α-syn delays OPC maturation by severely downregulating myelin-gene regulatory factor and myelin basic protein. Brain-derived neurotrophic factor was reduced in MSA models and its in vitro supplementation partially restored the phenotype. Taken together, efficacious induction of OPC maturation may open the window to restore glial and neuronal function in MSA.},
author = {Winner, Beate and May, Verena Elisabeth Luise and Ettle, Benjamin and Pöhler, Anne-Maria and Nuber, Silke and Ubhi, Kiren and Rockenstein, Edward and Wegner, Michael and Masliah, Eliezer and Winkler, Jürgen},
doi = {10.1016/j.neurobiolaging.2014.02.028},
faupublication = {yes},
journal = {Neurobiology of Aging},
pages = {2357-68},
peerreviewed = {Yes},
title = {α-{Synuclein} impairs oligodendrocyte progenitor maturation in multiple system atrophy.},
volume = {35},
year = {2014}
}
@article{faucris.252913862,
abstract = {Parkinson disease is characterized by the loss of dopaminergic neurons mainly in the substantia nigra. Accumulation of α-synuclein and cell loss has been also reported in many other brain regions including the hippocampus, where it might impair adult neurogenesis, contributing to nonmotor symptoms. However, the molecular mechanisms of these alterations are still unknown. In this report we show that α-synuclein-accumulating adult rat hippocampus neural progenitors present aberrant neuronal differentiation, with reduction of Notch1 expression and downstream signaling targets. We characterized a Notch1 proximal promoter that contains p53 canonical response elements. In vivo binding of p53 represses the transcription of Notch1 in neurons. Moreover, we demonstrated that α-synuclein directly binds to the DNA at Notch1 promoter vicinity and also interacts with p53 protein, facilitating or increasing Notch1 signaling repression, which interferes with maturation and survival of neural progenitors cells. This study provides a molecular basis for α-synuclein-mediated disruption of adult neurogenesis in Parkinson disease.},
author = {Desplats, Paula and Spencer, Brian and Crews, Leslie and Pathel, Pruthul and Morvinski-Friedmann, Dinorah and Kosberg, Kori and Roberts, Scott and Patrick, Christina and Winner, Beate and Winkler, Jürgen and Masliah, Eliezer},
doi = {10.1074/jbc.M112.354522},
faupublication = {no},
journal = {Journal of Biological Chemistry},
pages = {31691-702},
peerreviewed = {Yes},
title = {α-{Synuclein} induces alterations in adult neurogenesis in {Parkinson} disease models via p53-mediated repression of {Notch1}.},
volume = {287},
year = {2012}
}
@article{faucris.252783948,
abstract = {Early α-synuclein (α-Syn)-induced alterations are neurite pathologies resulting in Lewy neurites. α-Syn oligomers are a toxic species in synucleinopathies and are suspected to cause neuritic pathology. To investigate how α-Syn oligomers may be linked to aberrant neurite pathology, we modeled different stages of α-Syn aggregation in vitro and investigated the interplay of α-Syn aggregates with proteins involved in axonal transport. The interaction of wild type α-Syn (WTS) and α-Syn variants (E57K, A30P, and aSyn(30-110)) with kinesin, tubulin, and the microtubule (MT)-associated proteins, MAP2 and Tau, is stronger for multimers than for monomers. WTS seeds but not α-Syn oligomers significantly and dose-dependently reduced Tau-promoted MT assembly in vitro. In contrast, MT gliding velocity across kinesin-coated surfaces was significantly decreased in the presence of α-Syn oligomers but not WTS seeds or fibrils (aSyn(30-110) multimers). In a human dopaminergic neuronal cell line, mild overexpression of the oligomerizing E57K α-Syn variant significantly impaired neurite network morphology without causing profound cell death. In accordance with these findings, MT stability, neuritic kinesin, and neuritic kinesin-dependent cargoes were significantly reduced by the presence of α-Syn oligomers. In summary, different α-Syn species act divergently on the axonal transport machinery. These findings provide new insights into α-Syn oligomer-driven neuritic pathology as one of the earliest events in synucleinopathies.},
author = {Winner, Beate and Prots, Iryna and Brey, Stefanie and et al.},
author_hint = {Prots, Veber, Brey, Campioni, Buder, Riek, Böhm, Winner},
doi = {10.1074/jbc.M113.451815},
faupublication = {no},
journal = {Journal of Biological Chemistry},
pages = {21742-54},
peerreviewed = {Yes},
support_note = {Author relations incomplete. You may find additional data in field 'author{\_}hint'},
title = {α-{Synuclein} oligomers impair neuronal microtubule-kinesin interplay.},
volume = {288},
year = {2013}
}
@article{faucris.204520058,
abstract = {α-Synuclein (α-Syn) aggregation, proceeding from oligomers to fibrils, is one central hallmark of neurodegeneration in synucleinopathies. α-Syn oligomers are toxic by triggering neurodegenerative processes in in vitro and in vivo models. However, the precise contribution of α-Syn oligomers to neurite pathology in human neurons and the underlying mechanisms remain unclear. Here, we demonstrate the formation of oligomeric α-Syn intermediates and reduced axonal mitochondrial transport in human neurons derived from induced pluripotent stem cells (iPSC) from a Parkinson's disease patient carrying an α-Syn gene duplication. We further show that increased levels of α-Syn oligomers disrupt axonal integrity in human neurons. We apply an α-Syn oligomerization model by expressing α-Syn oligomer-forming mutants (E46K and E57K) and wild-type α-Syn in human iPSC-derived neurons. Pronounced α-Syn oligomerization led to impaired anterograde axonal transport of mitochondria, which can be restored by the inhibition of α-Syn oligomer formation. Furthermore, α-Syn oligomers were associated with a subcellular relocation of transport-regulating proteins Miro1, KLC1, and Tau as well as reduced ATP levels, underlying axonal transport deficits. Consequently, reduced axonal density and structural synaptic degeneration were observed in human neurons in the presence of high levels of α-Syn oligomers. Together, increased dosage of α-Syn resulting in α-Syn oligomerization causes axonal transport disruption and energy deficits, leading to synapse loss in human neurons. This study identifies α-Syn oligomers as the critical species triggering early axonal dysfunction in synucleinopathies.},
author = {Prots, Iryna and Grosch, Janina and Brazdis, Razvan-Marius and Simmnacher, Katrin and Veber, Vanesa and Havlicek, Steven and Hannappel, Christian and Krach, Florian and Krumbiegel, Mandy and Schuetz, Oliver and Reis, André and Wrasidlo, Wolfgang and Galasko, Douglas R. and Groemer, Teja W. and Masliah, Eliezer and Schlötzer-Schrehardt, Ursula and Xiang, Wei and Winkler, Jürgen and Winner, Beate},
doi = {10.1073/pnas.1713129115},
faupublication = {yes},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
keywords = {alpha-synuclein;oligomers;axonal transport;synucleinopathies;neurodegeneration},
note = {EVALuna2:34623},
pages = {7813-7818},
peerreviewed = {Yes},
title = {α-{Synuclein} oligomers induce early axonal dysfunction in human {iPSC}-based models of synucleinopathies},
volume = {115},
year = {2018}
}
@article{faucris.229749210,
abstract = {In cardiomyocytes, electrical activity is coupled to cellular contraction, thus exposing all proteins expressed in the sarcolemma to mechanical stress. The voltage-gated sodium channel Nav1.5 is the main contributor to the rising phase of the action potential in the heart. There is growing evidence that gating and kinetics of Nav1.5 are modulated by mechanical forces and pathogenic variants that affect mechanosensitivity have been linked to arrhythmias. Recently, the sodium channel β1 subunit has been described to stabilise gating against mechanical stress of Nav1.7 expressed in neurons. Here, we tested the effect of β1 and β3 subunits on mechanosensitivity of the cardiac Nav1.5. β1 amplifies stress-induced shifts of V1/2 of steady-state fast inactivation to hyperpolarised potentials (ΔV1/2: 6.2 mV without and 10.7 mV with β1 co-expression). β3, on the other hand, almost doubles stress-induced speeding of time to sodium current transient peak (Δtime to peak at − 30 mV: 0.19 ms without and 0.37 ms with β3 co-expression). Our findings may indicate that in cardiomyocytes, the interdependence of electrical activity and contraction is used as a means of fine tuning cardiac sodium channel function, allowing quicker but more strongly inactivating sodium currents under conditions of increased mechanical stress. This regulation may help to shorten action potential duration during tachycardia, to prevent re-entry phenomena and thus arrhythmias.},
author = {Maroni, Michele and Körner, Jannis and Schüttler, Jürgen and Winner, Beate and Lampert, Angelika and Eberhardt, Esther},
doi = {10.1007/s00424-019-02324-w},
faupublication = {yes},
journal = {Pflügers Archiv: European Journal of Physiology},
keywords = {Cardiac ion channel; Mechanosensitivity; Patch-clamp; Sodium channel},
note = {CRIS-Team Scopus Importer:2019-11-26},
pages = {1481-1492},
peerreviewed = {Yes},
title = {β1 and β3 subunits amplify mechanosensitivity of the cardiac voltage-gated sodium channel {Nav1}.5},
volume = {471},
year = {2019}
}
@article{faucris.262664621,
abstract = {As substantial constituents of the multiple myeloma (MM) microenvironment, pro-inflammatory macrophages have emerged as key promoters of disease progression, bone destruction, and immune impairment. We identify beta-2-microglobulin (β2m) as a driver in initiating inflammation in myeloma-associated macrophages (MAMs). Lysosomal accumulation of phagocytosed β2m promotes β2m amyloid aggregation in MAMs, resulting in lysosomal rupture and ultimately production of active interleukin-1β (IL-1β) and IL-18. This process depends on activation of the NLRP3 inflammasome after β2m accumulation, as macrophages from NLRP3-deficient mice lack efficient β2m-induced IL-1β production. Moreover, depletion or silencing of β2m in MM cells abrogates inflammasome activation in a murine MM model. Finally, we demonstrate that disruption of NLRP3 or IL-18 diminishes tumor growth and osteolytic bone destruction normally promoted by β2m-induced inflammasome signaling. Our results provide mechanistic evidence for β2m's role as an NLRP3 inflammasome activator during MM pathogenesis. Moreover, inhibition of NLRP3 represents a potential therapeutic approach in MM.},
author = {Hofbauer, Daniel and Mougiakakos, Dimitrios and Broggini, Luca and Zaiss, Mario and Büttner-Herold, Maike and Bach, Christian and Spriewald, Bernd and Neumann, Frank and Bisht, Savita and Nolting, Jens and Zeiser, Robert and Hamarsheh, Shaima'a and Eberhardt, Martin and Vera, Julio and Visentin, Cristina and De Luca, Chiara Maria Giulia and Moda, Fabio and Haskamp, Stefan and Flamann, Cindy and Böttcher, Martin and Bitterer, Katrin and Völkl, Simon and Mackensen, Andreas and Ricagno, Stefano and Bruns, Heiko},
doi = {10.1016/j.immuni.2021.07.002},
faupublication = {yes},
journal = {Immunity},
keywords = {inflammation; macrophages; multiple myeloma; NLRP3; phagocytosis; tumor-associated macrophages},
note = {CRIS-Team Scopus Importer:2021-08-13},
pages = {1772-1787.e9},
peerreviewed = {Yes},
title = {β2-microglobulin triggers {NLRP3} inflammasome activation in tumor-associated macrophages to promote multiple myeloma progression},
volume = {54},
year = {2021}
}
@inproceedings{faucris.248106946,
address = {LONDON},
author = {Kemmer, H. and Popp, B. and Verloes, A. and Horn, D. and Holtgrewe, M. and Zweier, Christiane and Ehmke, N.},
booktitle = {EUROPEAN JOURNAL OF HUMAN GENETICS},
faupublication = {yes},
note = {CRIS-Team WoS Importer:2021-01-22},
pages = {864-864},
peerreviewed = {unknown},
publisher = {SPRINGERNATURE},
title = {{Phenotypic} presentation of two additional individuals with heterozygous variants in {BRSK2}},
year = {2020}
}
@article{faucris.238605601,
abstract = {Purpose Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. Methods We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. Results We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. Conclusion We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies.},
author = {Castilla-Vallmanya, Laura and Selmer, Kaja K. and Dimartino, Clemantine and Rabionet, Raquel and Blanco-Sanchez, Bernardo and Yang, Sandra and Reijnders, Margot R. F. and Van Essen, Antonie J. and Oufadem, Myriam and Vigeland, Magnus D. and Stadheim, Barbro and Houge, Gunnar and Cox, Helen and Kingston, Helen and Clayton-Smith, Jill and Innis, Jeffrey W. and Iascone, Maria and Cereda, Anna and Gabbiadini, Sara and Chung, Wendy K. and Sanders, Victoria and Charrow, Joel and Bryant, Emily and Millichap, John and Vitobello, Antonio and Thauvin, Christel and Mau-Them, Frederic Tran and Faivre, Laurence and Lesca, Gaetan and Labalme, Audrey and Rougeot, Christelle and Chatron, Nicolas and Sanlaville, Damien and Christensen, Katherine M. and Kirby, Amelia and Lewandowski, Raymond and Gannaway, Rachel and Aly, Maha and Lehman, Anna and Clarke, Lorne and Graul-Neumann, Luitgard and Zweier, Christiane and Lessel, Davor and Lozic, Bernarda and Aukrust, Ingvild and Peretz, Ryan and Stratton, Robert and Smol, Thomas and Dieux-Coeslier, Anne and Meira, Joanna and Wohler, Elizabeth and Sobreira, Nara and Beaver, Erin M. and Heeley, Jennifer and Briere, Lauren C. and High, Frances A. and Sweetser, David A. and Walker, Melissa A. and Keegan, Catherine E. and Jayakar, Parul and Shinawi, Marwan and Kerstjens-Frederikse, Wilhelmina S. and Earl, Dawn L. and Siu, Victoria M. and Reesor, Emma and Yao, Tony and Hegele, Robert A. and Vaske, Olena M. and Rego, Shannon and Shapiro, Kevin A. and Wong, Brian and Gambello, Michael J. and Mcdonald, Marie and Karlowicz, Danielle and Colombo, Roberto and Serretti, Alessandro and Pais, Lynn and O'Donnell-Luria, Anne and Wray, Alison and Sadedin, Simon and Chong, Belinda and Tan, Tiong Y. and Christodoulou, John and White, Susan M. and Slavotinek, Anne and Barbouth, Deborah and Swols, Dayna Morel and Parisot, Melanie and Bole-Feysot, Christine and Nitschke, Patrick and Pingault, Veronique and Munnich, Arnold and Cho, Megan T. and Cormier-Daire, Valerie and Balcells, Susanna and Lyonnet, Stanislas and Grinberg, Daniel and Amiel, Jeanne and Urreizti, Roser and Gordon, Christopher T.},
doi = {10.1038/s41436-020-0792-7},
faupublication = {yes},
journal = {Genetics in Medicine},
note = {CRIS-Team WoS Importer:2020-05-22},
peerreviewed = {Yes},
title = {{Phenotypic} spectrum and transcriptomic profile associated with germline variants in {TRAF7}},
year = {2020}
}