Recurrent de novo mutations implicate novel genes underlying simplex autism risk
Open accessAbstract
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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Recent studies have reported additional individuals with ASD and/or NDD with de novo damaging variants in BRSK2, PAX5, NR4A2, RALGAPB, and DPP6.
“Recent studies have reported additional individuals with ASD and/or NDD with de novo damaging variants in these genes including BRSK2,27 PAX5,4,28 NR4A2,29,30 RALGAPB,7,31,32 and DPP6.5,33,34”
From Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes (2019) · cites this paper as [28]
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- Authors
- 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.
- Affiliations
- University of Washington (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Shendure, J.
- Eichler, E. E.
- ORCID
- Venue
- Nature Communications
- Published
- 2014-11-24
- Volume
- 5
- Issue
- 1
- Pages
- 5595-5595
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4249945
- OpenAlex
- W1979856142
- Cited by
- 336
- References
- 33
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 23 · 2023: 19 · 2022: 24 · 2021: 29 · 2020: 36 · 2019: 38 · 2018: 37 · 2017: 40 · 2016: 34 · 2015: 22
- FWCI
- 17.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Simons Foundation
- Simons Foundation Autism Research Initiative
- National Institutes of Health
- National Institute of Mental Health (R01MH101221)
- National Institute of General Medical Sciences (T32GM007266)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- autism spectrum disorder, de novo mutations, CHD2, SYNGAP1, TRIP12, PAX5, intellectual disability, seizures, autism subtypes, genetic aetiology
- MeSH terms
- Autistic Disorder, Base Sequence, Carrier Proteins, DNA-Binding Proteins, Family, Humans, Intelligence, Intelligence Tests, Mutation, Risk, Sequence Analysis, DNA, Genetic Predisposition to Disease, ras GTPase-Activating Proteins, Ubiquitin-Protein Ligases, PAX5 Transcription Factor
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