The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Recessive gene disruptions in autism spectrum disorder
Open accessAbstract
Autism spectrum disorder (ASD) affects up to 1 in 59 individuals 1. Genome-wide association and large-scale sequencing studies strongly implicate both common variants 2-4 and rare de novo variants 5-10 in ASD. Recessive mutations have also been implicated 11-14 but their contribution remains less well defined. Here we demonstrate an excess of biallelic loss-of-function and damaging missense mutations in a large ASD cohort, corresponding to approximately 5% of total cases, including 10% of females, consistent with a female protective effect. We document biallelic disruption of known or emerging recessive neurodevelopmental genes (CA2, DDHD1, NSUN2, PAH, RARB, ROGDI, SLC1A1, USH2A) as well as other genes not previously implicated in ASD including FEV (FEV transcription factor, ETS family member), which encodes a key regulator of the serotonergic circuitry. Our data refine estimates of the contribution of recessive mutation to ASD and suggest new paths for illuminating previously unknown biological pathways responsible for this condition.
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“In addition to dominant mutations, biallelic recessive mutations are descriptively more prevalent in autistic females than in autistic males237.”
From Sex and gender in neurodevelopmental conditions (2023) · cites this paper as [237]
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A method and server for predicting damaging missense mutations.
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Analysis of protein-coding genetic variation in 60,706 humans
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Self-citationGlutamate neurotoxicity and diseases of the nervous system
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MutationTaster evaluates disease-causing potential of sequence alterations
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Synaptic, transcriptional and chromatin genes disrupted in autism
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Self-citationDe novo mutations revealed by whole-exome sequencing are strongly associated with autism
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Fu, J. M., Satterstrom, F. K., Peng, M., Brand, H., Collins, R. L., Dong, S., Wamsley, B., Klei, L., Wang, L., Hao, S. P., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01104-0 · Cited by 640
Self-citationGenomic architecture of autism from comprehensive whole-genome sequence annotation
Trost, B., Thiruvahindrapuram, B., Chan, A. J. S., Engchuan, W., Higginbotham, E. J., Howe, J., Loureiro, L. O., Reuter, M. S., Roshandel, D., Whitney, J., et al. (2022) · Cell · doi:10.1016/j.cell.2022.10.009 · Cited by 287
Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications
Jiang, C.-C., Lin, L., Long, S., Ke, X., Fukunaga, K., Lu, Y., & Han, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01081-0 · Cited by 295
Sex and gender in neurodevelopmental conditions
Bölte, S., Neufeld, J., Marschik, P. B., Williams, Z. J., Gallagher, L., & Lai, M.-C. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00774-6 · Cited by 249
Genomics, convergent neuroscience and progress in understanding autism spectrum disorder
Willsey, H. R., Willsey, A. J., Wang, B., & State, M. W. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00576-7 · Cited by 239
Metadata
- Authors
- Autism Sequencing Consortium, Doan, R. N., Lim, E. T., De Rubeis, S., Betancur, C., Cutler, D. J., Chiocchetti, A. G., Overman, L. M., Soucy, A., Goetze, S., Freitag, C. M., Daly, M. J., Walsh, C. A., Buxbaum, J. D., & Yu, T. W.
- Affiliations
- Boston Children's Hospital (US)
- Centre National de la Recherche Scientifique (FR)
- Emory University (US)
- Goethe University Frankfurt (DE)
- Centre for Life (GB)
- Broad Institute (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Yu, Timothy W.
- ORCID
- Venue
- Nature Genetics
- Published
- 2019-06-17
- Volume
- 51
- Issue
- 7
- Pages
- 1092-1098
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC6629034
- OpenAlex
- W2952501183
- Cited by
- 159
- References
- 60
- Citations by year
- 2026: 13 · 2025: 11 · 2024: 27 · 2023: 21 · 2022: 31 · 2021: 26 · 2020: 27 · 2019: 3
- FWCI
- 12.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- HAL (submittedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust
- National Institutes of Health (5rc2mh089952-02, 1s10rr028832-01)
- Medical Research Council (MR/R006237/1)
- National Institute of Mental Health (U01MH100209, R01MH083565, U01MH111661, U01MH100229, R01MH113761, R01MH097849, U01MH111658, RC2-MH089952, U01MH100239, R56MH097849, U01MH111662, U01MH111660, U01MH100233)
- National Institute of Neurological Disorders and Stroke (T32NS007484)
- National Center for Research Resources (S10 RR028832)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U24HD093487, U19HD077671)
- 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 › Genomics and Rare Diseases
- Keywords
- autism spectrum disorder, recessive mutations, biallelic loss-of-function variants, neurodevelopmental genes, FEV, CA2, NSUN2, PAHs, retinoic acid receptor beta, SLC1A1, USH2A, rare variants
- MeSH terms
- Autism Spectrum Disorder, Exome Sequencing, Female, Genes, Recessive, Humans, Male, Cohort Studies, Genome, Human, Case-Control Studies, Genetic Predisposition to Disease, Mutation, Missense, Allelic Imbalance
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