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De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures

2018Journal article Open access
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dc.contributor.authorIto, Y
dc.contributor.authorCarss, KJ
dc.contributor.authorDuarte, ST
dc.contributor.authorHartley, T
dc.contributor.authorKeren, B
dc.contributor.authorKurian, MA
dc.contributor.authorMarey, I
dc.contributor.authorCharles, P
dc.contributor.authorMendonça, C
dc.contributor.authorNava, C
dc.contributor.authorPfundt, R
dc.contributor.authorSanchis-Juan, A
dc.contributor.authorvan Bokhoven, H
dc.contributor.authorvan Essen, A
dc.contributor.authorvan Ravenswaaij-Arts, C
dc.contributor.authorBoycott, KM
dc.contributor.authorKernohan, KD
dc.contributor.authorDyack, S
dc.contributor.authorRaymond, FL
dc.date.accessioned2020-05-15T13:51:30Z
dc.date.available2020-05-15T13:51:30Z
dc.date.issued2018
dc.description.abstractNext-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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAm J Hum Genet . 2018 Jul 5;103(1):144-153pt_PT
dc.identifier.doi10.1016/j.ajhg.2018.06.001pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3441
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherCell Presspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAdultpt_PT
dc.subjectFemalept_PT
dc.subjectHeterozygotept_PT
dc.subjectHumanspt_PT
dc.subjectIntellectual Disabilitypt_PT
dc.subjectMalept_PT
dc.subjectMutationpt_PT
dc.subjectSeizurespt_PT
dc.subjectWhole Exome Sequencingpt_PT
dc.subjectWiskott-Aldrich Syndrome Protein Familypt_PT
dc.subjectYoung Adultpt_PT
dc.subjectHDE NEU PEDpt_PT
dc.titleDe Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizurespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage153pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage144pt_PT
oaire.citation.titleAmerican journal of human geneticspt_PT
oaire.citation.volume103pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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