De novo variants in SUPT16H cause neurodevelopmental disorders associated with corpus callosum abnormalities
| Autor: | Dena R. Matalon, Roya Bina, Brieana Fregeau, Gunnar Houge, Kyra E. Stuurman, A. James Barkovich, Elliott H. Sherr, Renee Bend, Ingvild Aukrust, Jacqueline Joani Tarsitano, Hannah Warren, Roger E. Stevenson |
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| Přispěvatelé: | Clinical Genetics |
| Rok vydání: | 2020 |
| Předmět: |
Male
Adolescent Intellectual and Developmental Disabilities (IDD) In silico Mutation Missense Cell Cycle Proteins Biology Corpus callosum Medical and Health Sciences Article Corpus Callosum Clinical Research Seizures Intellectual Disability Exome Sequencing Intellectual disability Genetics medicine developmental 2.1 Biological and endogenous factors Humans Missense mutation Exome Genetic Predisposition to Disease Aetiology Preschool Child Gene Allele frequency Genetics (clinical) Genetics & Heredity Human Genome Neurosciences Brain Biological Sciences medicine.disease Phenotype other neurology Brain Disorders Chromatin Neurodevelopmental Disorders Child Preschool Mutation Female Missense Agenesis of Corpus Callosum Transcription Factors |
| Zdroj: | Journal of Medical Genetics, 57(7), 461-465. BMJ Publishing Group J Med Genet Journal of medical genetics, vol 57, iss 7 |
| ISSN: | 1468-6244 0022-2593 |
| Popis: | IntroductionWhole-exome sequencing (WES) has identified de novo variants in chromatin remodelling genes in patients with neurodevelopmental disorders (NDD). We report on a novel genetic discovery in chromatin remodelling in patients with NDD who also have corpus callosum (CC) anomalies.ObjectiveTo discover novel genes linked to both CC anomalies and NDD.MethodsClinical WES was performed for evaluation of NDD, identifying five patients with de novo variants in SUPT16H, a subunit of the FACT (facilitates chromatin transcription) complex. The clinical phenotypes, genetic results and brain MRIs were obtained and systematically reviewed. In silico protein function predictions were assessed and allele frequencies in control populations were compared.ResultsWe identified four patients with de novo missense variants in SUPT16H and one patient with a de novo deletion including SUPT16H. These variants were not reported in the updated Genome Aggregation Database. When assayable, all protein products were predicted to be damaging. Symptoms included intellectual disability, autistic features, minor dysmorphic features and seizures. Anomalies of the CC were seen in all three patients with available brain imaging.ConclusionOur findings implicate the gene SUPT16H in a novel disorder characterised by neurodevelopmental deficits and CC anomalies. |
| Databáze: | OpenAIRE |
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