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De novo variants in neurodevelopmental disorders with epilepsy

Heyne, HO; Singh, T; Stamberger, H; Abou Jamra, R; Caglayan, H; Craiu, D; De Jonghe, P; ... Lemke, JR; + view all (2018) De novo variants in neurodevelopmental disorders with epilepsy. Nature Genetics , 50 (7) pp. 1048-1053. 10.1038/s41588-018-0143-7. Green open access

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Abstract

Epilepsy is a frequent feature of neurodevelopmental disorders (NDDs), but little is known about genetic differences between NDDs with and without epilepsy. We analyzed de novo variants (DNVs) in 6,753 parent–offspring trios ascertained to have different NDDs. In the subset of 1,942 individuals with NDDs with epilepsy, we identified 33 genes with a significant excess of DNVs, of which SNAP25 and GABRB2 had previously only limited evidence of disease association. Joint analysis of all individuals with NDDs also implicated CACNA1E as a novel disease-associated gene. Comparing NDDs with and without epilepsy, we found missense DNVs, DNVs in specific genes, age of recruitment, and severity of intellectual disability to be associated with epilepsy. We further demonstrate the extent to which our results affect current genetic testing as well as treatment, emphasizing the benefit of accurate genetic diagnosis in NDDs with epilepsy.

Type: Article
Title: De novo variants in neurodevelopmental disorders with epilepsy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-018-0143-7
Publisher version: https://doi.org/10.1038/s41588-018-0143-7
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, AUTISM SPECTRUM DISORDER, INTELLECTUAL DISABILITY, KCNQ2 ENCEPHALOPATHY, SEQUENCE VARIANTS, ILAE COMMISSION, HUMAN-DISEASE, MUTATIONS, CLASSIFICATION, TERMINOLOGY, PREVALENCE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10056021
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