Recurrent de novo mutations implicate novel genes underlying simplex autism risk

B. J. O'Roak; H. A. Stessman; E. A. Boyle; K. T. Witherspoon; B. Martin; C. Lee; L. Vives; C. Baker; J. B. Hiatt; D. A. Nickerson; R. Bernier; J. Shendure; E. E. Eichler

doi:10.1038/ncomms6595

Recurrent de novo mutations implicate novel genes underlying simplex autism risk

B. J. O'Roak, H. A. Stessman, E. A. Boyle, K. T. Witherspoon, B. Martin, C. Lee, L. Vives, C. Baker, J. B. Hiatt, D. A. Nickerson, R. Bernier, J. Shendure, E. E. Eichler

Molecular & Medical Genetics

Research output: Contribution to journal › Article

162 Scopus citations

Abstract

Autism spectrum disorder (ASD) has a strong but complex genetic component. Here we report on the resequencing of 64 candidate neurodevelopmental disorder risk genes in 5,979 individuals: 3,486 probands and 2,493 unaffected siblings. We find a strong burden of de novo point mutations for these genes and specifically implicate nine genes. These include CHD2 and SYNGAP1, genes previously reported in related disorders, and novel genes TRIP12 and PAX5. We also show that mutation carriers generally have lower IQs and enrichment for seizures. These data begin to distinguish genetically distinct subtypes of autism important for aetiological classification and future therapeutics.

Original language	English (US)
Article number	5595
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6595
State	Published - 2014

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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O'Roak, B. J., Stessman, H. A., Boyle, E. A., Witherspoon, K. T., Martin, B., Lee, C., Vives, L., Baker, C., Hiatt, J. B., Nickerson, D. A., Bernier, R., Shendure, J., & Eichler, E. E. (2014). Recurrent de novo mutations implicate novel genes underlying simplex autism risk. Nature communications, 5, [5595]. https://doi.org/10.1038/ncomms6595

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abstract = "Autism spectrum disorder (ASD) has a strong but complex genetic component. Here we report on the resequencing of 64 candidate neurodevelopmental disorder risk genes in 5,979 individuals: 3,486 probands and 2,493 unaffected siblings. We find a strong burden of de novo point mutations for these genes and specifically implicate nine genes. These include CHD2 and SYNGAP1, genes previously reported in related disorders, and novel genes TRIP12 and PAX5. We also show that mutation carriers generally have lower IQs and enrichment for seizures. These data begin to distinguish genetically distinct subtypes of autism important for aetiological classification and future therapeutics.",

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