De Novo Mutations in the Gene Encoding the Synaptic Scaffolding Protein SHANK3 in Patients Ascertained for Schizophrenia

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Apr 14

PMID 20385823

Citations 204

Authors

Julie Gauthier

Nathalie Champagne

Ronald G Lafreniere

Lan Xiong

Dan Spiegelman

Edna Brustein

Mathieu Lapointe

Huashan Peng

Melanie Cote

Anne Noreau

Fadi F Hamdan

Anjene M Addington

Judith L Rapoport

Lynn E DeLisi

Marie-Odile Krebs

Ridha Joober

Ferid Fathalli

Faycal Mouaffak

Ali P Haghighi

Christian Neri

Marie-Pierre Dube

Mark E Samuels

Claude Marineau

Eric A Stone

Philip Awadalla

Philip A Barker

Salvatore Carbonetto

Pierre Drapeau

Guy A Rouleau

Affiliations

Soon will be listed here.

Abstract

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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