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TY - JOUR AU - Heyne, Henrike O. AU - Singh, Tarjinder AU - Stamberger, Hannah AU - Abou Jamra, Rami AU - Caglayan, Hande AU - Craiu, Dana AU - De Jonghe, Peter AU - Guerrini, Renzo AU - Helbig, Katherine L. AU - Koeleman, Bobby P. C. AU - Kosmicki, Jack A. AU - Linnankivi, Tarja AU - May, Patrick AU - Muhle, Hiltrud AU - Møller, Rikke S. AU - Neubauer, Bernd A. AU - Palotie, Aarno AU - Pendziwiat, Manuela AU - Striano, Pasquale AU - Tang, Sha AU - Wu, Sitao AU - Afawi, Zaid AU - de Kovel, Carolien AU - Dimova, Petia AU - Djémié, Tania AU - Endziniene, Milda AU - Hoffman-Zacharska, Dorota AU - Jähn, Johanna AU - Korff, Christian AU - Lehesjoki, Anna-Elina AU - Marini, Carla AU - Müller, Stefanie H. AU - Pal, Deb AU - Schwarz, Niklas AU - Selmer, Kaja AU - Serratosa, Jose AU - Stephani, Ulrich AU - Štěrbová, Katalin AU - Suls, Arvid AU - Syrbe, Steffen AU - Talvik, Inga AU - Tang, Shan AU - von Spiczak, Sarah AU - Zara, Federico AU - Poduri, Annapurna AU - Weber, Yvonne G. AU - Weckhuysen, Sarah AU - Sisodiya, Sanjay M. AU - Daly, Mark J. AU - Helbig, Ingo AU - Lal, Dennis AU - Lemke, Johannes R. AU - EuroEPINOMICS RES Consortium PY - 2018 DA - 2018/07/01 TI - De novo variants in neurodevelopmental disorders with epilepsy JO - Nature Genetics SP - 1048 EP - 1053 VL - 50 IS - 7 AB - 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. SN - 1546-1718 UR - https://doi.org/10.1038/s41588-018-0143-7 DO - 10.1038/s41588-018-0143-7 ID - Heyne2018 ER -