Variants in PUS7 Cause Intellectual Disability with Speech Delay, Microcephaly, Short Stature, and Aggressive Behavior.

Détails

ID Serval
serval:BIB_27BE43BD14F2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Variants in PUS7 Cause Intellectual Disability with Speech Delay, Microcephaly, Short Stature, and Aggressive Behavior.
Périodique
American journal of human genetics
Auteur(s)
de Brouwer APM, Abou Jamra R., Körtel N., Soyris C., Polla D.L., Safra M., Zisso A., Powell C.A., Rebelo-Guiomar P., Dinges N., Morin V., Stock M., Hussain M., Shahzad M., Riazuddin S., Ahmed Z.M., Pfundt R., Schwarz F., de Boer L., Reis A., Grozeva D., Raymond F.L., Riazuddin S., Koolen D.A., Minczuk M., Roignant J.Y., van Bokhoven H., Schwartz S.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Statut éditorial
Publié
Date de publication
06/12/2018
Peer-reviewed
Oui
Volume
103
Numéro
6
Pages
1045-1052
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
We describe six persons from three families with three homozygous protein truncating variants in PUS7: c.89_90del (p.Thr30Lysfs <sup>∗</sup> 20), c.1348C>T (p.Arg450 <sup>∗</sup> ), 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.
Mots-clé
Adolescent, Aggression/physiology, Animals, Child, Drosophila melanogaster/genetics, Dwarfism/genetics, Exons/genetics, Female, Gene Knockout Techniques/methods, Genetic Variation/genetics, Homozygote, Humans, Intellectual Disability/genetics, Language Development Disorders/genetics, Male, Microcephaly/genetics, Pedigree, Phenotype, RNA, Messenger/genetics, RNA, Transfer/genetics, Drosophila melanogaster, aggressive behavior, growth delay, intellectual disability, mRNA substrates, microcephaly, neurodevelopmental delay, pseudouridylation, speech delay, tRNA
Pubmed
Web of science
Création de la notice
28/10/2019 12:33
Dernière modification de la notice
29/10/2019 6:26
Données d'usage