Ito, Y., Carss, K.J., Duarte, S.T. et al. (18 more authors) (2018) De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures. The American Journal of Human Genetics, 103 (1). pp. 144-153. ISSN 0002-9297
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Crown Copyright © 2018. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | WASF1; WAVE1 complex; neurodevelopmental disorder; autism; seizures; lamellipodia; actin cytoskeleton; recurrent de novo truncating mutations; developmental delay |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Mar 2019 17:08 |
Last Modified: | 20 Mar 2019 17:08 |
Status: | Published |
Publisher: | Elsevier (Cell Press) |
Refereed: | Yes |
Identification Number: | 10.1016/j.ajhg.2018.06.001 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:143926 |
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