ArticleNature2018
De novo mutations in regulatory elements in neurodevelopmental disorders.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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.
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Who cites it
150 citing papers in PubMed, 307 citations in OpenAlex.
- A nationwide prospective randomized trial for diagnosing developmental disorders demonstrates genome sequencing outperforms standard of care.Genome medicine · 2026Trial
- Mechanisms underlying disease-causing variants in promoters and enhancers.Nature genetics · 2026Review
- De novo structural variants in autism spectrum disorder disrupt distal regulatory interactions of neuronal genes.Genome research · 2026Article
- Postnatal relevance of HOXA5 transcription factor in cerebellum-associated behaviors and disorders.Behavioral and brain functions : BBF · 2026Article
- Decoding common and rare noncoding variant effects across cellular and developmental contexts.Nature genetics · 2026Article
- Non-coding structural variants disrupt FOXG1 transcriptional regulation in early neurodevelopment.Nature communications · 2026Article
- Variant-resolved prediction of context-specific isoform variation with a graph-based attention model.Cell genomics · 2026Article
- Screening Candidate Genes for Body Size Traits in Dongfeng Sika Deer Bucks Based on Genome-Wide Association Analysis.Biology · 2026Article
- Review
- A combined genomic arrhythmia propensity score delineates cumulative risk.Cell reports. Medicine · 2025Article
- Identifying deleterious noncoding variation through gain and loss of CTCF binding activity.American journal of human genetics · 2025Article
- Genetic Variants Associated with Suspected Neonatal Hypoxic Ischaemic Encephalopathy: A Study in a South African Context.International journal of molecular sciences · 2025Article
- Mapping the regulatory effects of common and rare non-coding variants across cellular and developmental contexts in the brain and heart.bioRxiv : the preprint server for biology · 2025Article
- Rapid and quantitative functional interrogation of human enhancer variant activity in live mice.Nature communications · 2025Article
- JAK/STAT in human diseases: a common axis in immunodeficiencies and hematological disorders.Frontiers in immunology · 2025Review
- Benchmarking of variant pathogenicity prediction methods using a population genetics approach.Bioinformatics advances · 2025Article
- Review
- Noncoding variants are a rare cause of recessive developmental disorders in trans with coding variants.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Autism Spectrum Disorder Pathogenesis-A Cross-Sectional Literature Review Emphasizing Molecular Aspects.International journal of molecular sciences · 2024Review
- A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.Nature communications · 2024Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders.
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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.