Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373782" target="_blank" >RIV/00216208:11130/17:10373782 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1038/nn.4589" target="_blank" >https://doi.org/10.1038/nn.4589</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/nn.4589" target="_blank" >10.1038/nn.4589</a>

Result language

angličtina

Original language name

Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10600 - Biological sciences

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Neuroscience

ISSN

1097-6256

e-ISSN

—

Volume of the periodical

20

Issue of the periodical within the volume

8

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

1043-1051

UT code for WoS article

000406298900005

EID of the result in the Scopus database

2-s2.0-85026416277