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PMID: 17999366 Published · ppublish English Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Contribution of SHANK3 mutations to autism spectrum disorder.

American journal of human genetics ·Vol. 81 ·No. 6 ·2007-12-00 ·Pages 1289-97

Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, Zwaigenbaum L, Fernandez B, Roberts W, Szatmari P, Scherer SW

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.

MeSH Terms
Autistic Disorder Carrier Proteins/genetics Chromosome Mapping Chromosomes, Human, Pair 14 Chromosomes, Human, Pair 20 Chromosomes, Human, Pair 22 DNA/chemistry,genetics Female Genetic Variation Humans Male Mutation Nerve Tissue Proteins Pedigree Sequence Deletion Translocation, Genetic
Chemicals
Carrier Proteins Nerve Tissue Proteins SHANK3 protein, human DNA
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Moessner Rainald
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, M5G 1L7, Canada.
Marshall Christian R
Sutcliffe James S
Skaug Jennifer
Pinto Dalila
Vincent John
Zwaigenbaum Lonnie
Fernandez Bridget
Roberts Wendy
Szatmari Peter
Scherer Stephen W
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
1537-6605
DOI
10.1086/522590
Published
2007-12-00
Epub
2007-00-16
Pages
1289-97
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC2276348
Subset
IM
Grants
NIMH NIH HHS · R01 MH061009 · United States
NIMH NIH HHS · MH061009 · United States
External Links
PubMed source DOI: 10.1086/522590 PMC Full Text View journal details
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