ArticlePLoS genetics2014
De novo mutations in moderate or severe intellectual disability.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 222 papers, 5 of them syntheses that pooled it.
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Who cites it
222 citing papers in PubMed, 5 syntheses or guidelines pooled it, 415 citations in OpenAlex.
- Pooled it
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- Genome-wide DNA methylation meta-analysis in the brains of suicide completers.Translational psychiatry · 2020Pooled it
- High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.American journal of human genetics · 2017Pooled it
- Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome.European journal of human genetics : EJHG · 2017Pooled it
- A De Novo heterozygous frameshift mutation identified in BCL11B causes neurodevelopmental disorder by whole exome sequencing.Molecular genetics & genomic medicine · 2019Trial
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- A case of Incontinentia Pigmenti associated with concurrentFrontiers in medicine · 2026Article
- Systematic evaluation of de novo mutation calling tools using whole genome sequencing data.Briefings in bioinformatics · 2025Article
- Novel MYH10 heterozygous variants associated to a syndrome combining mainly ptosis and ocular coloboma expand the MYH10 related phenotypes.European journal of human genetics : EJHG · 2025Article
- GRIN2B-related neurodevelopmental disorders: genotype-phenotype correlations and therapeutic implications.Orphanet journal of rare diseases · 2025Article
- Structural basis of nonmuscle myosin-2 autoinhibition mechanisms.bioRxiv : the preprint server for biology · 2025Article
- SETBP1 variants outside the degron disrupt DNA-binding, transcription and neuronal differentiation capacity to cause a heterogeneous neurodevelopmental disorder.Nature communications · 2025Article
- NoncodingiScience · 2025Article
- Complimentary vertebratebioRxiv : the preprint server for biology · 2025Article
- The Identification of Proteolytic Substrates of Calpain-5 with N-Terminomics.International journal of molecular sciences · 2025Article
162 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
17 authors at 6 institutions in 1 country.
Funding
Abstract
Genetics is believed to have an important role in intellectual disability (ID). Recent studies have emphasized the involvement of de novo mutations (DNMs) in ID but the extent to which they contribute to its pathogenesis and the identity of the corresponding genes remain largely unknown. Here, we report a screen for DNMs in subjects with moderate or severe ID. We sequenced the exomes of 41 probands and their parents, and confirmed 81 DNMs affecting the coding sequence or consensus splice sites (1.98 DNMs/proband). We observed a significant excess of de novo single nucleotide substitutions and loss-of-function mutations in these cases compared to control subjects, suggesting that at least a subset of these variations are pathogenic. A total of 12 likely pathogenic DNMs were identified in genes previously associated with ID (ARID1B, CHD2, FOXG1, GABRB3, GATAD2B, GRIN2B, MBD5, MED13L, SETBP1, TBR1, TCF4, WDR45), resulting in a diagnostic yield of ∼29%. We also identified 12 possibly pathogenic DNMs in genes (HNRNPU, WAC, RYR2, SET, EGR1, MYH10, EIF2C1, COL4A3BP, CHMP2A, PPP1CB, VPS4A, PPP2R2B) that have not previously been causally linked to ID. Interestingly, no case was explained by inherited mutations. Protein network analysis indicated that the products of many of these known and candidate genes interact with each other or with products of other ID-associated genes further supporting their involvement in ID. We conclude that DNMs represent a major cause of moderate or severe ID.
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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.