Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/107476
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains
Author: Geisheker, M.
Heymann, G.
Wang, T.
Coe, B.
Turner, T.
Stessman, H.
Hoekzema, K.
Kvarnung, M.
Shaw, M.
Friend, K.
Liebelt, J.
Barnett, C.
Thompson, E.
Haan, E.
Guo, H.
Anderlid, B.
Nordgren, A.
Lindstrand, A.
Vandeweyer, G.
Alberti, A.
et al.
Citation: Nature Neuroscience, 2017; 20(8):1043-1051
Publisher: Nature Publishing Group
Issue Date: 2017
ISSN: 1097-6256
1546-1726
Statement of
Responsibility: 
Madeleine R Geisheker ... Marie Shaw ... Kathryn Friend ... Jan Liebelt, Christopher Barnett, Elizabeth M Thompson, Eric Haan ... Jozef Gecz ... et al.
Abstract: Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,688 patients with NDD identified 21 new patients with identical missense mutations. One recurrent site substitution (p.A636T) occurs in a glutamate receptor subunit, GRIA1. This same amino acid substitution in the homologous but distinct mouse glutamate receptor subunit Grid2 is associated with Lurcher ataxia. Phenotypic follow-up in five individuals with GRIA1 mutations shows evidence of specific learning disabilities and autism. Overall, we find significant clustering of de novo mutations in 200 genes, highlighting specific functional domains and synaptic candidate genes important in NDD pathology.
Keywords: Humans; Genetic Predisposition to Disease; Receptors, Glutamate; Receptors, AMPA; Autistic Disorder; Amino Acid Sequence; Mutation, Missense; Female; Male; Exome
Description: Published online 19 June 2017
Rights: © The Author(s). © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
RMID: 0030071555
DOI: 10.1038/nn.4589
Appears in Collections:Genetics publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.