| Literature DB >> 29942082 |
Henrike O Heyne1,2,3,4, Tarjinder Singh5,6, Hannah Stamberger7,8,9, Rami Abou Jamra10, Hande Caglayan11, Dana Craiu12, Peter De Jonghe7,8,9, Renzo Guerrini13, Katherine L Helbig14, Bobby P C Koeleman15, Jack A Kosmicki5,6, Tarja Linnankivi16, Patrick May17, Hiltrud Muhle18, Rikke S Møller19,20, Bernd A Neubauer21, Aarno Palotie5, Manuela Pendziwiat18, Pasquale Striano22, Sha Tang23, Sitao Wu23, Annapurna Poduri24, Yvonne G Weber25, Sarah Weckhuysen7,8,9, Sanjay M Sisodiya26,27, Mark J Daly5,6, Ingo Helbig14,18, Dennis Lal5,6,28, Johannes R Lemke29.
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.Entities:
Mesh：
Year: 2018 PMID： 29942082 DOI： 10.1038/s41588-018-0143-7
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330