Strong association of de novo copy number mutations with autism

Jonathan Sebat, B. Lakshmi, Dheeraj Malhotra, Jennifer Troge, Christa Lese-Martin, Tom Walsh, Boris Yamrom, Seungtai Yoon, Alex Krasnitz, Jude Kendall, Anthony Leotta, Deepa Pai, Ray Zhang, Yoon Ha Lee, James Hicks, Sarah J. Spence, Annette T. Lee, Kaija Puura, Terho Lehtimäki, David LedbetterPeter K. Gregersen, Joel Bregman, James S. Sutcliffe, Vaidehi Jobanputra, Wendy Chung, Dorothy Warburton, Mary Claire King, David Skuse, Daniel H. Geschwind, T. Conrad Gilliam, Kenny Ye, Michael Wigler

Research output: Contribution to journalArticlepeer-review

2139 Scopus citations


We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized.

Original languageEnglish (US)
Pages (from-to)445-449
Number of pages5
Issue number5823
StatePublished - Apr 20 2007

ASJC Scopus subject areas

  • General


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