ArticleMolecular psychiatry2017
Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.
Article in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 3 of them syntheses that pooled it.
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Who cites it
145 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Diagnostic and clinical utility of exome sequencing and chromosomal microarray in children with GDD/iD: a meta-analysis.Annals of medicine · 2026Pooled it
- Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Pooled it
- Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Pooled it
- Targeting the DNHD1‑HDAC6 axis inactivates prostate cancer cell aggressivenessOncology reports · 2026Article
- A Candidate Gene for Cerebro-Oculo-Nasal Syndrome: A Zinc-Finger GeneMolecular syndromology · 2026Article
- A severe neurodevelopmental syndrome linked to a South Asian founder variant in the UFMylation adaptor CDK5RAP3.Acta neuropathologica · 2026Article
- Long-Term Follow-Up of a Patient with a Novel HomozygousNeurology international · 2026Article
- First reported case of developmental dysplasia of the hips in a child with 3M syndrome: a case report.Journal of surgical case reports · 2026Article
- Dominant and recessive ATOH1 variants cause distinct neurodevelopmental disorders with hearing loss.American journal of human genetics · 2026Article
- Bi-allelic variants in neuronal adhesion molecule astrotactin 1 gene ASTN1 cause diverse neurodevelopmental disorders.American journal of human genetics · 2026Article
- Quality control and signaling pathways at stalled ribosomes.Experimental & molecular medicine · 2026Review
- Investigation of Genetic Aetiology in Intellectual Developmental Disorder with Trio-Whole Exome Sequencing Approach.Noro psikiyatri arsivi · 2026Article
- A Multi-Center Study: Developing a Nomogram for Predicting Genetic Results of Trio-Based Whole-Exome Sequencing (Trio-WES) in Diagnosing Children with Syndromic Neurodevelopmental Disorders (s-NDDs).International journal of general medicine · 2026Article
- Editorial: Rare genetic disorders associated with intellectual disability.Frontiers in psychiatry · 2026Article
- Pathogenic homozygous PLCZ1 mutation reduces sperm protein levels with a simulated reduction of PIP2 binding: a case report.Reproduction & fertility · 2026Article
- Recessive genomic and phenotypic variation in consanguineous families with cerebral palsy.medRxiv : the preprint server for health sciences · 2025Article
- Cerebellar dysfunction in a mouse model of childhood-onset manganese-induced dystonia parkinsonism.Neurobiology of disease · 2025Article
- Article
- SEL1L-HRD1-mediated ERAD in mammals.Nature cell biology · 2025Review
- The genetic spectrum features of 2261 Chinese children with epilepsy and intellectual disability.BMC medicine · 2025Article
85 more citing papers are in PubMed but not listed here.
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Authors and funding
48 authors.
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Abstract
Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA2B and CLIP1), thus supporting their involvement in ID pathogenesis. Our results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.
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