Recurrent de novo mutations implicate novel genes underlying simplex autism risk

Nat Commun. 2014 Nov 24:5:5595. doi: 10.1038/ncomms6595.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder / genetics*
  • Base Sequence
  • Carrier Proteins / genetics
  • DNA-Binding Proteins / genetics
  • Family
  • Genetic Predisposition to Disease*
  • Humans
  • Intelligence / genetics
  • Intelligence Tests
  • Mutation
  • PAX5 Transcription Factor / genetics
  • Risk
  • Sequence Analysis, DNA
  • Ubiquitin-Protein Ligases / genetics
  • ras GTPase-Activating Proteins / genetics


  • CHD2 protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • PAX5 Transcription Factor
  • PAX5 protein, human
  • SYNGAP1 protein, human
  • ras GTPase-Activating Proteins
  • TRIP12 protein, human
  • Ubiquitin-Protein Ligases