Imperial College London
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DrCarolynMillar

Faculty of Medicine, Department of Immunology and Inflammation

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 2153c.millar

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ito:2018:10.1016/j.ajhg.2018.06.001,
author = {Ito, Y and Carss, KJ and Duarte, ST and Hartley, T and Keren, B and Kurian, MA and Marey, I and Charles, P and Mendonça, C and Nava, C and Pfundt, R and Sanchis-Juan, A and van, Bokhoven H and van, Essen A and van, Ravenswaaij-Arts C and NIHR, BioResource and Care4Rare, Canada Consortium and Boycott, KM and Kernohan, KD and Dyack, S and Raymond, FL},
doi = {10.1016/j.ajhg.2018.06.001},
journal = {American Journal of Human Genetics},
pages = {144--153},
title = {De Novo truncating mutations in WASF1 cause intellectual disability with seizures},
url = {http://dx.doi.org/10.1016/j.ajhg.2018.06.001},
volume = {103},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Ito,Y
AU  - Carss,KJ
AU  - Duarte,ST
AU  - Hartley,T
AU  - Keren,B
AU  - Kurian,MA
AU  - Marey,I
AU  - Charles,P
AU  - Mendonça,C
AU  - Nava,C
AU  - Pfundt,R
AU  - Sanchis-Juan,A
AU  - van,Bokhoven H
AU  - van,Essen A
AU  - van,Ravenswaaij-Arts C
AU  - NIHR,BioResource
AU  - Care4Rare,Canada Consortium
AU  - Boycott,KM
AU  - Kernohan,KD
AU  - Dyack,S
AU  - Raymond,FL
DO  - 10.1016/j.ajhg.2018.06.001
EP  - 153
PY  - 2018///
SN  - 0002-9297
SP  - 144
TI  - De Novo truncating mutations in WASF1 cause intellectual disability with seizures
T2  - American Journal of Human Genetics
UR  - http://dx.doi.org/10.1016/j.ajhg.2018.06.001
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29961568
UR  - http://hdl.handle.net/10044/1/73539
VL  - 103
ER  -
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