Contribution of SHANK3 Mutations to Autism Spectrum Disorder

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2007 Nov 14

PMID 17999366

Citations 327

Authors

Rainald Moessner

Christian R Marshall

James S Sutcliffe

Jennifer Skaug

Dalila Pinto

John Vincent

Lonnie Zwaigenbaum

Bridget Fernandez

Wendy Roberts

Peter Szatmari

Stephen W Scherer

Affiliations

Soon will be listed here.

Abstract

Mutations in SHANK3, which encodes a synaptic scaffolding protein, have been described in subjects with an autism spectrum disorder (ASD). To assess the quantitative contribution of SHANK3 to the pathogenesis of autism, we determined the frequency of DNA sequence and copy-number variants in this gene in 400 ASD-affected subjects ascertained in Canada. One de novo mutation and two gene deletions were discovered, indicating a contribution of 0.75% in this cohort. One additional SHANK3 deletion was characterized in two ASD-affected siblings from another collection, which brings the total number of published mutations in unrelated ASD-affected families to seven. The combined data provide support that haploinsufficiency of SHANK3 can cause a monogenic form of autism in sufficient frequency to warrant consideration in clinical diagnostic testing.

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