Ito, Yoko, Carss, Keren J, Duarte, Sofia T, Hartley, Taila, Keren, Boris, Kurian, Manju A, Marey, Isabelle, Charles, Perinne, Mendonca, Carla, Nava, Caroline et al (show 9 more authors)
(2018)
De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.
AMERICAN JOURNAL OF HUMAN GENETICS, 103 (1).
pp. 144-153.
Abstract
Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NIHR BioResource, Care4Rare Canada Consortium, Humans, Seizures, Heterozygote, Mutation, Adult, Female, Male, Wiskott-Aldrich Syndrome Protein Family, Young Adult, Intellectual Disability, Exome Sequencing |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 03 Sep 2019 15:43 |
| Last Modified: | 03 Feb 2023 05:03 |
| DOI: | 10.1016/j.ajhg.2018.06.001 |
| Open Access URL: | https://www.sciencedirect.com/science/article/pii/... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3053342 |
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