Title: De novo variants in neurodevelopmental disorders with epilepsy.

Authors: Henrike O Heyne, Tarjinder Singh, Hannah Stamberger, Rami Abou Jamra, Hande Cağlayan, Dana Craiu, Peter De Jonghe, Renzo Guerrini, Katherine L Helbig, Bobby P C Koeleman, Jack A Kosmicki, Tarja Linnankivi, Patrick May, Hiltrud Muhle, Rikke S Møller, Bernd A Neubauer, Aarno Palotie, Manuela Pendziwiat, Pasquale Striano, Sha Tang, Sitao Wu, , Annapurna Poduri, Yvonne G Weber, Sarah Weckhuysen, Sanjay M Sisodiya, Mark J Daly, Ingo Helbig, Dennis Lal, Johannes R Lemke

Journal, date & volume: Nat Genet, 2018Jul, 50, 1048-1053

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/29942082

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.