Contribution of SHANK3 Mutations to Autism Spectrum Disorder

Am J Hum Genet. 2007 Dec;81(6):1289-97. doi: 10.1086/522590. Epub 2007 Oct 16.

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder
  • Carrier Proteins / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 20
  • Chromosomes, Human, Pair 22
  • DNA / chemistry
  • DNA / genetics
  • Female
  • Genetic Variation*
  • Humans
  • Male
  • Mutation*
  • Nerve Tissue Proteins
  • Pedigree
  • Sequence Deletion
  • Translocation, Genetic

Substances

  • Carrier Proteins
  • Nerve Tissue Proteins
  • SHANK3 protein, human
  • DNA