ArticleNature2012
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,300 papers, 8 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1,300 citing papers in PubMed, 8 syntheses or guidelines pooled it, 2,212 citations in OpenAlex.
- Optimal dosage of group-based organized physical activity for enhancing social abilities in autistic children: insights from a multilevel meta-analysis.The international journal of behavioral nutrition and physical activity · 2025Pooled it
- Presymptomatic Biological, Structural, and Functional Diagnostic Biomarkers of Autism Spectrum Disorder.Journal of neurochemistry · 2025Pooled it
- Global autism prevalence, and exploring Montessori as a practical educational solution: a systematic review.Frontiers in psychiatry · 2025Pooled it
- A assessment of the effects of parental age on the development of autism in children: a systematic review and a meta-analysis.BMC psychology · 2024Pooled it
- Bridging Genetic Insights with Neuroimaging in Autism Spectrum Disorder-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Meta-analysis of 46,000 germline de novo mutations linked to human inherited disease.Human genomics · 2024Pooled it
- Mapping autism's research landscape: trends in autism screening and its alignment with sustainable development goals.Frontiers in psychiatry · 2023Pooled it
- Correlation between Phenotype and Genotype in CTNNB1 Syndrome: A Systematic Review of the Literature.International journal of molecular sciences · 2022Pooled it
- Review
- Whole-exome sequencing in individuals with obsessive-compulsive disorder and chronic tic disorders identifies 36 large-effect risk genes.Nature neuroscience · 2026Article
- Diagnostic Yield of Whole Exome Sequencing in Autism Spectrum Disorder Patients at a Tertiary Center in Saudi Arabia.Journal of autism and developmental disorders · 2026Article
- The mMolecular psychiatry · 2026Article
- Glial heterogeneity shapes region-specific angiogenesis and neurovascular integrity in the CNS.Science advances · 2026Article
- Rationale and Methods for the Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center at Columbia University.Pediatric research · 2026Article
- Monoallelic and biallelic KDM5A variants identified in patients with autism spectrum disorder.HGG advances · 2026Article
- Molecular Acrobats: How CHD Remodelers Shape the Genetic Playground to License Cell Identity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Itgb3 expression is developmentally regulated in pyramidal neurons of mouse cortex and hippocampus.Neuroscience letters · 2026Article
- A Developmental Neuroimmune Cascade Model of Autism Spectrum Disorder.International journal of molecular sciences · 2026Review
- CUL3-Related Neurodevelopmental Disorder: Expanding the Prenatal Phenotype.Prenatal diagnosis · 2026Article
- Highly Constrained Kinetic Models for Single-Cell Gene Expression Analysis.bioRxiv : the preprint server for biology · 2026Article
1,240 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 2 institutions in 1 country.
Funding
Abstract
It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown. Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported. Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD. Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.