title: Contribution of SHANK3 mutations to autism spectrum disorder.
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.
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, M5G 1L7, Canada.
authors.forename: Rainald
authors.initials: R
authors.lastname: Moessner
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.forename: James S
authors.initials: JS
authors.lastname: Sutcliffe
authors.forename: Jennifer
authors.initials: J
authors.lastname: Skaug
authors.forename: Dalila
authors.initials: D
authors.lastname: Pinto
authors.forename: John
authors.initials: J
authors.lastname: Vincent
authors.forename: Lonnie
authors.initials: L
authors.lastname: Zwaigenbaum
authors.forename: Bridget
authors.initials: B
authors.lastname: Fernandez
authors.forename: Wendy
authors.initials: W
authors.lastname: Roberts
authors.forename: Peter
authors.initials: P
authors.lastname: Szatmari
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D001321:Autistic Disorder; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002890:Chromosomes, Human, Pair 20; D002892:Chromosomes, Human, Pair 22; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins; D010375:Pedigree; D017384:Sequence Deletion; D014178:Translocation, Genetic
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human; D004247:DNA