ArticleNature2012
Patterns and rates of exonic de novo mutations in autism spectrum disorders.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,058 papers, 3 of them syntheses that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1,058 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,788 citations in OpenAlex.
- 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
- Analysing an allelic series of rare missense variants of CACNA1I in a Swedish schizophrenia cohort.Brain : a journal of neurology · 2022Pooled it
- Early environmental risk factors for neurodevelopmental disorders - a systematic review of twin and sibling studies.Development and psychopathology · 2021Pooled it
- Integrin-Talin axis regulates mechanosensory presynaptic development and behavioral habituation to mechanical stimulation.G3 (Bethesda, Md.) · 2026Article
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- Genetic Diagnosis in Epilepsy: Implications for Clinical Management.Current neurology and neuroscience reports · 2026Review
- Comprehensive Assessment of the KDM2B-Associated Neurodevelopmental Disorder and the 12q24.31 Microdeletion Syndrome.Clinical genetics · 2026Article
- Uncoupling memory impairments from autism-associated behaviors in Chd2 deficient mice.Molecular psychiatry · 2026Article
- Rationale and Methods for the Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center at Columbia University.Pediatric research · 2026Article
- Advancing risk gene discovery across the allele frequency spectrum.HGG advances · 2026Review
- Temporal and Cell-Specific Regulation of Synaptic Homeostasis by the Chromatin Remodeler Chd1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- A Novel Variant of theGenes · 2026Article
- Autism-like phenotypes and increased NMDAR2D expression in mice with KDM5B histone lysine demethylase deficiency.Science advances · 2026Article
- CN-RNN: a Deep Learning Framework for Copy Number Variation Detection with Exome Sequencing Data.bioRxiv : the preprint server for biology · 2026Article
- The emerging role of gene therapy in autism spectrum disorder.Discover mental health · 2026Review
- Article
- Cerebellar Abnormalities: A Component of Autism Pathophysiology.Medicina (Kaunas, Lithuania) · 2026Review
- BRD1 haploinsufficiency alters early neuronal programming and disrupts maturation in human induced glutamatergic neurons.Research square · 2026Article
998 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
59 authors at 14 institutions in 2 countries.
Funding
Abstract
Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified. To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivity among themselves and to previous ASD genes as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors.
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What OpenQuestion holds
Registered trials
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.