Association between microdeletion and microduplication at 16p11.2 and autism

Academic Article

Abstract

  • Background: Autism spectrum disorder is a heritable developmental disorder in which chromosomal abnormalities are thought to play a role. Methods: As a first component of a genomewide association study of families from the Autism Genetic Resource Exchange (AGRE), we used two novel algorithms to search for recurrent copy-number variations in genotype data from 751 multiplex families with autism. Specific recurrent de novo events were further evaluated in clinical-testing data from Children's Hospital Boston and in a large population study in Iceland. Results: Among the AGRE families, we observed five instances of a de novo deletion of 593 kb on chromosome 16p11.2. Using comparative genomic hybridization, we observed the identical deletion in 5 of 512 children referred to Children's Hospital Boston for developmental delay, mental retardation, or suspected autism spectrum disorder, as well as in 3 of 299 persons with autism in an Icelandic population; the deletion was also carried by 2 of 18,834 unscreened Icelandic control subjects. The reciprocal duplication of this region occurred in 7 affected persons in AGRE families and 4 of the 512 children from Children's Hospital Boston. The duplication also appeared to be a high-penetrance risk factor. Conclusions: We have identified a novel, recurrent microdeletion and a reciprocal microduplication that carry substantial susceptibility to autism and appear to account for approximately 1% of cases. We did not identify other regions with similar aggregations of large de novo mutations. Copyright © 2008 Massachusetts Medical Society.
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    Digital Object Identifier (doi)

    Author List

  • Weiss LA; Shen Y; Korn JM; Arking DE; Miller DT; Fossdal R; Saemundsen E; Stefansson H; Ferreira MAR; Green T
  • Start Page

  • 667
  • End Page

  • 675
  • Volume

  • 358
  • Issue

  • 7