Contribution of SHANK3 mutations to autism spectrum disorder.
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.
Moessner
Rainald
R
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, M5G 1L7, Canada.
Marshall
Christian R
CR
Sutcliffe
James S
JS
Skaug
Jennifer
J
Pinto
Dalila
D
Vincent
John
J
Zwaigenbaum
Lonnie
L
Fernandez
Bridget
B
Roberts
Wendy
W
Szatmari
Peter
P
Scherer
Stephen W
SW
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
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human; D004247:DNA