Reference : De novo Variants in Neurodevelopmental Disorders with Epilepsy
Scientific journals : Article
Life sciences : Genetics & genetic processes
Human health sciences : Neurology
Systems Biomedicine
De novo Variants in Neurodevelopmental Disorders with Epilepsy
Heyne, Henrike O. []
Singh, Tarijinder []
Stamberger, Hannah []
Jamra, Rami Abou []
Caglayan, Hande []
Craiu, Dana []
De Jonghe, Peter []
Guerrini, Renzo []
Helbig, Katherine L. []
Koeleman, Bobby P.C. []
Kosmicki, Jack A. []
Linnankivi, Tarja []
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Muhle, Hiltrud []
Møller, Rikke S. []
Neubauer, Bernd A. []
Palotie, Aarno []
Pendziwiat, Manuela []
Striano, Pasquale []
Tang, Sha []
Wu, Sitao []
Poduri, Annapurna []
Weber, Yvonne G. []
Weckhuysen, Sarah []
Sisodiya, Sanjay M. []
Daly, Mark []
Helbig, Ingo []
Lal, Dennis []
Lemke, Johannes R. []
Nature Genetics
Nature Publishing Group
Yes (verified by ORBilu)
New York
[en] Epilepsy ; Neurodevelopment ; de novo mutations
[en] Epilepsy is a frequent feature of neurodevelopmental disorders (NDD) but little is known about genetic differences between NDD with and without epilepsy. We analyzed de novo variants (DNV) in 6753 parent-offspring trios ascertained for different NDD. In the subset of 1942 individuals with NDD with epilepsy, we identified 33 genes with a significant excess of DNV, of which SNAP25 and GABRB2 had previously only limited evidence for disease association. Joint analysis of all individuals with NDD also implicated CACNA1E as a novel disease gene. Comparing NDD with and without epilepsy, we found missense DNV, DNV in specific genes, age of recruitment and severity of intellectual disability to be associated with epilepsy. We further demonstrate to what extent our results impact current genetic testing as well as treatment, emphasizing the benefit of accurate genetic diagnosis in NDD with epilepsy.
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)

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