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Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.

ABSTRACT: SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders.

SUBMITTER: Durand CM

PROVIDER: S-EPMC2082049 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.

Durand Christelle M CM Betancur Catalina C Boeckers Tobias M TM Bockmann Juergen J Chaste Pauline P Fauchereau Fabien F Nygren Gudrun G Rastam Maria M Gillberg I Carina IC Anckarsäter Henrik H Sponheim Eili E Goubran-Botros Hany H Delorme Richard R Chabane Nadia N Mouren-Simeoni Marie-Christine MC de Mas Philippe P Bieth Eric E Rogé Bernadette B Héron Delphine D Burglen Lydie L Gillberg Christopher C Leboyer Marion M Bourgeron Thomas T

Nature genetics 20061217 1

SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spec ...[more]

PMID: 17173049

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De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia.

Project description:Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding the synaptic protein SHANK3 in 285 controls and 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X and R536W) were identified in two families, one being found in three affected brothers, suggesting germline mosaicism. Zebrafish and rat hippocampal neuron assays revealed behavior and differentiation defects resulting from the R1117X mutant. As mutations in SHANK3 were previously reported in autism, the occurrence of SHANK3 mutations in subjects with a schizophrenia phenotype suggests a molecular genetic link between these two neurodevelopmental disorders.

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Contribution of SHANK3 mutations to autism spectrum disorder.

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SHANK3 gene mutations associated with autism facilitate ligand binding to the Shank3 ankyrin repeat region.

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