Periodical
De novo variants in SUPT16Hcause neurodevelopmental disorders associated with corpus callosum abnormalities
| العنوان: | De novo variants in SUPT16Hcause neurodevelopmental disorders associated with corpus callosum abnormalities |
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| المؤلفون: | Bina, Roya, Matalon, Dena, Fregeau, Brieana, Tarsitano, Jacqueline Joani, Aukrust, Ingvild, Houge, Gunnar, Bend, Renee, Warren, Hannah, Stevenson, Roger E, Stuurman, Kyra Eva, Barkovich, A James, Sherr, Elliott H. |
| المصدر: | Journal of Medical Genetics (JMG); 2020, Vol. 57 Issue: 7 p461-465, 5p |
| مستخلص: | 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 SUPT16Hand 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 SUPT16Hin a novel disorder characterised by neurodevelopmental deficits and CC anomalies. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00222593 14686244 |
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| DOI: | 10.1136/jmedgenet-2019-106193 |