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. 2008 Feb 14;358(7):667-75.
doi: 10.1056/NEJMoa075974. Epub 2008 Jan 9.

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

Lauren A Weiss  1 , Yiping Shen, Joshua M Korn, Dan E Arking, David T Miller, Ragnheidur Fossdal, Evald Saemundsen, Hreinn Stefansson, Manuel A R Ferreira, Todd Green, Orah S Platt, Douglas M Ruderfer, Christopher A Walsh, David Altshuler, Aravinda Chakravarti, Rudolph E Tanzi, Kari Stefansson, Susan L Santangelo, James F Gusella, Pamela Sklar, Bai-Lin Wu, Mark J Daly; Autism Consortium
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Free article

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

Lauren A Weiss et al. N Engl J Med. .
Free 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.

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Comment in

  • A hot spot of genetic instability in autism.
    Eichler EE, Zimmerman AW. Eichler EE, et al. N Engl J Med. 2008 Feb 14;358(7):737-9. doi: 10.1056/NEJMe0708756. Epub 2008 Jan 9. N Engl J Med. 2008. PMID: 18184953 No abstract available.

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