Genetic analysis of VCP and WASH complex genes in a German cohort of sporadic ALS-FTD patients
Türk M, Schröder R, Khuller K, Hofmann A, Berwanger C, Ludolph AC, Dekomien G, Mueller K, Weishaupt JH, Thiel C, Clemen CS (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 56
Pages Range: 213.e1-213.e5
DOI: 10.1016/j.neurobiolaging.2017.04.023
Abstract
Mutations of the human valosin-containing protein, p97 (VCP) and Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex genes cause motor neuron and cognitive impairment disorders. Here, we analyzed a cohort of German patients with sporadic amyotrophic lateral sclerosis and frontotemporal lobar degeneration comorbidity (ALS/FTD) for VCP and WASH complex gene mutations. Next-generation panel sequencing of VCP, WASH1, FAM21C, CCDC53, SWIP, strumpellin, F-actin capping protein of muscle Z-line alfa 1 (CAPZA1), and CAPZB genes was performed in 43 sporadic ALS/FTD patients. Subsequent analyses included Sanger sequencing, in silico analyses, real-time PCR, and CCDC53 immunoblotting. We identified 1 patient with the heterozygous variant c.26C>T in CAPZA1, predicted to result in p.Ser9Leu, and a second with the heterozygous start codon variant c.2T>C in CCDC53. In silico analysis predicted structural changes in the N-terminus of CAPZ?1, which may interfere with CAPZ?:CAPZ? dimerization. Though the translation initiation codon of CCDC53 is mutated, real-time PCR and immunoblotting did neither reveal any evidence for a CCDC53 haploinsufficiency nor for aberrant CCDC53 protein species. Moreover, a disease-causing C9orf72 repeat expansion mutation was later on identified in this patient. Thus, with the exception of a putatively pathogenic heterozygous c.26C>T CAPZA1 variant, our genetic analysis did not reveal mutations in VCP and the remaining WASH complex subunits.
Authors with CRIS profile
Matthias Türk
Lehrstuhl für Neuropathologie
Rolf Schröder
Professur für Neuropathologie
Christian Thiel
Medizinische Fakultät
Involved external institutions
Universität Ulm
Germany (DE)
Ruhr-Universität Bochum (RUB)
Germany (DE)
Griffith University
Australia (AU)
Universität zu Köln
Germany (DE)
Germany (DE)
Ruhr-Universität Bochum (RUB)
Germany (DE)
Griffith University
Australia (AU)
Universität zu Köln
Germany (DE)
How to cite
APA:
Türk, M., Schröder, R., Khuller, K., Hofmann, A., Berwanger, C., Ludolph, A.C.,... Clemen, C.S. (2017). Genetic analysis of VCP and WASH complex genes in a German cohort of sporadic ALS-FTD patients. Neurobiology of Aging, 56, 213.e1-213.e5. https://doi.org/10.1016/j.neurobiolaging.2017.04.023
MLA:
Türk, Matthias, et al. "Genetic analysis of VCP and WASH complex genes in a German cohort of sporadic ALS-FTD patients." Neurobiology of Aging 56 (2017): 213.e1-213.e5.
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