ArticleGenetics in medicine : official journal of the American College of Medical Genetics2020
De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 31 citations in OpenAlex.
- Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing.The Journal of clinical investigation · 2021Trial
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- Pathogenic mutations in clathrin heavy chain disrupt synapse architecture and learning iniScience · 2026Article
- Missense variants in DPYSL5 associated with neurodevelopmental disorders and brain malformations cause impaired neuronal maturation in vitro.Molecular psychiatry · 2026Article
- Intellectual developmental disorder 56 associated with novel variants in the clathrin heavy chain encoding CLTC gene and brief review of the literature.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Transcriptomic and proteomic analyses of SH-SY5Y neuroblastoma cells treated with amisulpride.Acta neuropsychiatrica · 2025Article
- Mosaic CLTC pathogenic variant causing focal epilepsy with normal intelligence.Epileptic disorders : international epilepsy journal with videotape · 2024Article
- Neurodevelopmental and synaptic defects in DNAJC6 parkinsonism, amenable to gene therapy.Brain : a journal of neurology · 2024Article
- Reply to: Partially Levodopa-Responsive Parkinsonism in a Carrier of a Novel Pathogenic CLTC Variant.Movement disorders clinical practice · 2024Article
- Identifying molecular subgroups of patients with preeclampsia through bioinformatics.Frontiers in cardiovascular medicine · 2024Article
- A novel de novo CLTC variant altering RNA splicing causes fetal developmental abnormalities.BMC medical genomics · 2023Article
- Improvement of Movement Disorder and Neurodevelopment under Selegiline in a CLTC-Deficient Patient.Movement disorders clinical practice · 2023Article
- Comparative Genomic Analysis Identifies Great-Ape-Specific Structural Variants and Their Evolutionary Relevance.Molecular biology and evolution · 2023Article
- Contribution of the dihydropyrimidinase-like proteins family in synaptic physiology and in neurodevelopmental disorders.Frontiers in neuroscience · 2023Review
- The recurrent pathogenic Pro890Leu substitution in CLTC causes a generalized defect in synaptic transmission inFrontiers in molecular neuroscience · 2023Article
- Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model.Journal of translational medicine · 2022Article
- Novel CLTC variants cause new brain and kidney phenotypes.Journal of human genetics · 2022Article
- Isobutyryl-CoA dehydrogenase deficiency associated with autism in a girl without an alternative genetic diagnosis by trio whole exome sequencing: A case report.Molecular genetics & genomic medicine · 2021Article
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Authors and funding
30 authors at 11 institutions in 7 countries.
Funding
Abstract
purposeTo delineate the genotype-phenotype correlation in individuals with likely pathogenic variants in the CLTC gene.
methodsWe describe 13 individuals with de novo CLTC variants. Causality of variants was determined by using the tolerance landscape of CLTC and computer-assisted molecular modeling where applicable. Phenotypic abnormalities observed in the individuals identified with missense and in-frame variants were compared with those with nonsense or frameshift variants in CLTC.
resultsAll de novo variants were judged to be causal. Combining our data with that of 14 previously reported affected individuals (n = 27), all had intellectual disability (ID), ranging from mild to moderate/severe, with or without additional neurologic, behavioral, craniofacial, ophthalmologic, and gastrointestinal features. Microcephaly, hypoplasia of the corpus callosum, and epilepsy were more frequently observed in individuals with missense and in-frame variants than in those with nonsense and frameshift variants. However, this difference was not significant.
conclusionsThe wide phenotypic variability associated with likely pathogenic CLTC variants seems to be associated with allelic heterogeneity. The detailed clinical characterization of a larger cohort of individuals with pathogenic CLTC variants is warranted to support the hypothesis that missense and in-frame variants exert a dominant-negative effect, whereas the nonsense and frameshift variants would result in haploinsufficiency.
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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.