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

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156 Scopus citations


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 languageEnglish (US)
Article number5595
JournalNature Communications
StatePublished - 2014


All Science Journal Classification (ASJC) codes

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

Cite this

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].