ArticleJournal of medical genetics2014
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.
Article in Journal of medical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 3 of them syntheses that pooled it.
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Who cites it
147 citing papers in PubMed, 3 syntheses or guidelines pooled it, 272 citations in OpenAlex.
- Retinoic Acid-Induced 1 Gene and Neuropsychiatric Diseases: A Systematic Review.Expert reviews in molecular medicine · 2025Pooled it
- Guideline recommendations for diagnosis and clinical management of Ring14 syndrome-first report of an ad hoc task force.Orphanet journal of rare diseases · 2017Guideline
- Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome.European journal of human genetics : EJHG · 2017Pooled it
- Genome sequencing for the diagnosis of intellectual disability as a paradigm for rare diseases in the French healthcare setting: the prospective DEFIDIAG study.Genome medicine · 2025Trial
- Diagnostic pathways in developmental disorders: a decade-apart comparison of two multicenter cohorts (2012-2022).European journal of human genetics : EJHG · 2026Article
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- Individuals with reported and novel KDM5C variants present with seizures, a feature recapitulated in a Drosophila model.Human molecular genetics · 2026Article
- The missense mutation Y65C in PQBP1 causes microcephaly and cognitive deficits through a combination of partial loss-of-function and gain-of-function effects.Nature communications · 2026Article
- Renpenning syndrome caused by the c.459_462delAGAG mutation in PQBP1: a case report and literature review.Frontiers in genetics · 2026Article
- The Role of mRNA Alternative Processing in Mammalian Neurodevelopment.International journal of molecular sciences · 2025Review
- An impaired glycolysis induces ATP deficiency and reduced cell respiration in stem cells of patients with autism spectrum disorders.Scientific reports · 2025Article
- Contribution of families using the GenIDA database to the description of MED13L syndrome and literature review.Journal of neurodevelopmental disorders · 2025Review
- Novel De Novo Intronic Variant of SYNGAP1 Associated With the Neurodevelopmental Disorders.Molecular genetics & genomic medicine · 2025Article
- Perturbed synaptic adhesion molecules signaling in neurodevelopmental disorders: The impact of metal neurotoxicity.Ibrain · 2025Review
- Ultrasound combined with molecular genetics to diagnose hereditary Renpenning syndrome in early pregnancy: a case report.Frontiers in genetics · 2025Article
- Review
- Trio-whole exome sequencing reveals the importance of de novo variants in children with intellectual disability and developmental delay.Scientific reports · 2024Article
- Novel splicing variant and gonadal mosaicism in DYRK1A gene identified by whole-genome sequencing in multiplex autism spectrum disorder families.Neurogenetics · 2024Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
47 authors at 17 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntellectual disability (ID) is characterised by an extreme genetic heterogeneity. Several hundred genes have been associated to monogenic forms of ID, considerably complicating molecular diagnostics. Trio-exome sequencing was recently proposed as a diagnostic approach, yet remains costly for a general implementation.
methodsWe report the alternative strategy of targeted high-throughput sequencing of 217 genes in which mutations had been reported in patients with ID or autism as the major clinical concern. We analysed 106 patients with ID of unknown aetiology following array-CGH analysis and other genetic investigations. Ninety per cent of these patients were males, and 75% sporadic cases.
resultsWe identified 26 causative mutations: 16 in X-linked genes (ATRX, CUL4B, DMD, FMR1, HCFC1, IL1RAPL1, IQSEC2, KDM5C, MAOA, MECP2, SLC9A6, SLC16A2, PHF8) and 10 de novo in autosomal-dominant genes (DYRK1A, GRIN1, MED13L, TCF4, RAI1, SHANK3, SLC2A1, SYNGAP1). We also detected four possibly causative mutations (eg, in NLGN3) requiring further investigations. We present detailed reasoning for assigning causality for each mutation, and associated patients' clinical information. Some genes were hit more than once in our cohort, suggesting they correspond to more frequent ID-associated conditions (KDM5C, MECP2, DYRK1A, TCF4). We highlight some unexpected genotype to phenotype correlations, with causative mutations being identified in genes associated to defined syndromes in patients deviating from the classic phenotype (DMD, TCF4, MECP2). We also bring additional supportive (HCFC1, MED13L) or unsupportive (SHROOM4, SRPX2) evidences for the implication of previous candidate genes or mutations in cognitive disorders.
conclusionsWith a diagnostic yield of 25% targeted sequencing appears relevant as a first intention test for the diagnosis of ID, but importantly will also contribute to a better understanding regarding the specific contribution of the many genes implicated in ID and autism.
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