Recurrent de novo mutations implicate novel genes underlying simplex autism risk View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-11-24

AUTHORS

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

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. More... »

PAGES

5595-5595

References to SciGraph publications

  • 2014-10-29. The contribution of de novo coding mutations to autism spectrum disorder in NATURE
  • 2014-05-20. The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses in MOLECULAR AUTISM
  • 2014-09-01. A framework for the interpretation of de novo mutation in human disease in NATURE GENETICS
  • 2014-09-14. Refining analyses of copy number variation identifies specific genes associated with developmental delay in NATURE GENETICS
  • 2012-04-04. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations in NATURE
  • 2013-05-26. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 in NATURE GENETICS
  • 2014-04-22. CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems in JOURNAL OF NEURODEVELOPMENTAL DISORDERS
  • 2011-05-15. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations in NATURE GENETICS
  • 2012-04-04. De novo mutations revealed by whole-exome sequencing are strongly associated with autism in NATURE
  • 2014-01-22. De novo mutations in schizophrenia implicate synaptic networks in NATURE
  • 2014-01-16. The role of de novo mutations in the genetics of autism spectrum disorders in NATURE REVIEWS GENETICS
  • 2012-04-04. Patterns and rates of exonic de novo mutations in autism spectrum disorders in NATURE
  • 2014-02-16. A SWI/SNF related autism syndrome caused by de novo mutations in ADNP in NATURE GENETICS
  • 2013-08-11. De novo mutations in the classic epileptic encephalopathies in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms6595

    DOI

    http://dx.doi.org/10.1038/ncomms6595

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25418537


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