Copy number variations associated with autism spectrum disorders contribute to a spectrum of neurodevelopmental disorders

Genet Med. 2010 Nov;12(11):694-702. doi: 10.1097/GIM.0b013e3181f0c5f3.


Purpose: Autism spectrum disorders represent a range of neurodevelopmental disorders that have been shown to have a strong genetic etiological component. Microarray-based comparative genomic hybridization and other molecular cytogenetic techniques are discovering an increasing number of copy number variations in individuals with autism spectrum disorder.

Methods: We examined the yield of abnormal microarray-based comparative genomic hybridization findings in our laboratory for individuals referred for testing for autism spectrum disorder. We also examined the presence of autistic features among 151 additional individuals who were referred for microarray-based comparative genomic hybridization testing for indications other than autism spectrum disorder but had genomic alterations overlapping those found in cases referred for autism spectrum disorder.

Results: We identified 1461 individuals referred for testing for autism spectrum disorder, with likely significant abnormalities reported in approximately 11.6% of individuals analyzed with whole-genome arrays. These abnormalities include alterations that encompass novel candidate genes such as SNTG2, SOX5, HFE, and TRIP38. A minority of individuals with overlapping abnormalities (19%) had autistic features, and many of the copy number variations identified in our study are inherited (69% among those found in individuals with autism spectrum disorder).

Conclusions: Our results suggest these copy number variations are one of multiple factors contributing to the development of an autism spectrum disorder phenotype. Additionally, the broad phenotypic spectrum of the patients with these copy number variations suggests that these copy number variations are not autism spectrum disorder-specific but likely more generally impair neurodevelopment.

MeSH terms

  • Child Development Disorders, Pervasive / diagnosis*
  • Child, Preschool
  • Gene Deletion
  • Gene Dosage*
  • Genetic Loci
  • Genetic Variation*
  • Genome-Wide Association Study
  • Humans