Variants in PUS7 Cause Intellectual Disability with Speech Delay, Microcephaly, Short Stature, and Aggressive Behavior
De Brouwer APM, Abou Jamra R, Koertel N, Soyris C, Polla DL, Safra M, Zisso A, Powell CA, Rebelo-Guiomar P, Dinges N, Morin V, Stock M, Hussain M, Shahzad M, Riazuddin S, Ahmed ZM, Pfundt R, Schwarz F, De Boer L, Reis A, Grozeva D, Raymond FL, Riazuddin S, Koolen DA, Minczuk M, Roignant JY, Van Bokhoven H, Schwartz S (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 103
Pages Range: 1045-1052
Journal Issue: 6
DOI: 10.1016/j.ajhg.2018.10.026
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.
Authors with CRIS profile
Involved external institutions
Institut für Molekulare Biologie gGmbH / Institute of Molecular Biology (IMB)
Germany (DE)
Radboud University Nijmegen
Netherlands (NL)
Weizmann Institute of Science
Israel (IL)
University of Cambridge
United Kingdom (GB)
Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU)
Pakistan (PK)
University of Maryland
United States (USA) (US)
University of the Punjab
Pakistan (PK)
Germany (DE)
Radboud University Nijmegen
Netherlands (NL)
Weizmann Institute of Science
Israel (IL)
University of Cambridge
United Kingdom (GB)
Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU)
Pakistan (PK)
University of Maryland
United States (USA) (US)
University of the Punjab
Pakistan (PK)
How to cite
APA:
De Brouwer, A.P.M., Abou Jamra, R., Koertel, N., Soyris, C., Polla, D.L., Safra, M.,... Schwartz, S. (2018). Variants in PUS7 Cause Intellectual Disability with Speech Delay, Microcephaly, Short Stature, and Aggressive Behavior. American Journal of Human Genetics, 103(6), 1045-1052. https://doi.org/10.1016/j.ajhg.2018.10.026
MLA:
De Brouwer, Arjan P. M., et al. "Variants in PUS7 Cause Intellectual Disability with Speech Delay, Microcephaly, Short Stature, and Aggressive Behavior." American Journal of Human Genetics 103.6 (2018): 1045-1052.
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