ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Variant recurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense variants.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
21 citing papers in PubMed, 29 citations in OpenAlex.
- Reduced expression of Brain Expressed X-linked genes in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Family-Based GWAS of Cognitive Endophenotypes Reveals Genetic Architecture of Memory and Executive Function in Alzheimer's Disease.Current issues in molecular biology · 2026Article
- Function and regulation of the mitochondrial stress response.Nature structural & molecular biology · 2026Review
- De NovoInternational journal of molecular sciences · 2025Review
- Germline mutations in a G protein identify signaling cross-talk in T cells.Science (New York, N.Y.) · 2024Article
- Targeted protein degradation: from mechanisms to clinic.Nature reviews. Molecular cell biology · 2024Review
- A recurrent missense variant in the E3 ubiquitin ligase substrate recognition subunit FEM1B causes a rare syndromic neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Systematic reanalysis of genomic data by diagnostic laboratories: a scoping review of ethical, economic, legal and (psycho)social implications.European journal of human genetics : EJHG · 2024Article
- Structural insights into the ubiquitylation strategy of the oligomeric CRL2The EMBO journal · 2024Article
- Evaluating the use of paralogous protein domains to increase data availability for missense variant classification.Genome medicine · 2023Article
- Multidisciplinary molecular consultation increases the diagnosis of pediatric epileptic encephalopathy and neurodevelopmental disorders.Molecular genetics & genomic medicine · 2023Article
- Comparative Analysis of the GNAI Family Genes in Glioblastoma through Transcriptomics and Single-Cell Technologies.Cancers · 2023Article
- Defining E3 ligase-substrate relationships through multiplex CRISPR screening.Nature cell biology · 2023Article
- Landscape of mSWI/SNF chromatin remodeling complex perturbations in neurodevelopmental disorders.Nature genetics · 2023Article
- A novel de novo FEM1C variant is linked to neurodevelopmental disorder with absent speech, pyramidal signs and limb ataxia.Human molecular genetics · 2023Article
- Diagnostic performance of automated, streamlined, daily updated exome analysis in patients with neurodevelopmental delay.Molecular medicine (Cambridge, Mass.) · 2022Article
- Novel CLTC variants cause new brain and kidney phenotypes.Journal of human genetics · 2022Article
- Motor, epileptic, and developmental phenotypes in genetic disorders affecting G protein coupled receptors-cAMP signaling.Frontiers in neurology · 2022Review
- Article
- Case Report: A NovelFrontiers in neurology · 2021Article
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 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeNext-generation sequencing has revealed the major impact of de novo variants (DNVs) in developmental disorders (DD) such as intellectual disability, autism, and epilepsy. However, a substantial fraction of these predicted pathogenic DNVs remains challenging to distinguish from background DNVs, notably the missense variants acting via nonhaploinsufficient mechanisms on specific amino acid residues. We hypothesized that the detection of the same missense variation in at least two unrelated individuals presenting with a similar phenotype could be a powerful approach to reveal novel pathogenic variants.
methodsWe looked for variations independently present in both our database of >1200 solo exomes and in denovo-db, a large, publicly available collection of de novo variants identified in patients with DD.
resultsThis approach identified 30 variants with strong evidence of pathogenicity, including variants already classified as pathogenic or probably pathogenic by our team, and also several new variants of interest in known OMIM genes or in novel genes. We identified FEM1B and GNAI2 as good candidate genes for syndromic intellectual disability and confirmed the implication of ACTL6B in a neurodevelopmental disorder.
conclusionAnnotation of local variants with denovo-db can highlight missense variants with high potential for pathogenicity, both facilitating the time-consuming reanalysis process and allowing novel DD gene discoveries.
Indexed as
Identifiers
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.