Heyne, Henrike O., Singh, Tarjinder ORCID: 0000-0003-0601-6815, Stamberger, Hannah, Abou Jamra, Rami, Caglayan, Hande, Craiu, Dana, De Jonghe, Peter, Guerrini, Renzo, Helbig, Katherine L., Koeleman, Bobby P. C., Kosmicki, Jack A., Linnankivi, Tarja, May, Patrick ORCID: 0000-0001-8698-3770, Muhle, Hiltrud, Moller, Rikke S., Neubauer, Bernd A., Palotie, Aarno, Pendziwiat, Manuela, Striano, Pasquale ORCID: 0000-0002-6065-1476, Tang, Sha, Wu, Sitao, Poduri, Annapurna, Weber, Yvonne G., Weckhuysen, Sarah ORCID: 0000-0003-2878-1147, Sisodiya, Sanjay M., Daly, Mark J., Helbig, Ingo, Lal, Dennis and Lemke, Johannes R. (2018). De novo variants in neurodevelopmental disorders with epilepsy. Nature Genet., 50 (7). S. 1048 - 1056. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Heyne, Henrike O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singh, TarjinderUNSPECIFIEDorcid.org/0000-0003-0601-6815UNSPECIFIED
Stamberger, HannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abou Jamra, RamiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caglayan, HandeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Craiu, DanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Jonghe, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guerrini, RenzoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helbig, Katherine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koeleman, Bobby P. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kosmicki, Jack A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linnankivi, TarjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
May, PatrickUNSPECIFIEDorcid.org/0000-0001-8698-3770UNSPECIFIED
Muhle, HiltrudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moller, Rikke S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neubauer, Bernd A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palotie, AarnoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pendziwiat, ManuelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Striano, PasqualeUNSPECIFIEDorcid.org/0000-0002-6065-1476UNSPECIFIED
Tang, ShaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, SitaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poduri, AnnapurnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, Yvonne G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weckhuysen, SarahUNSPECIFIEDorcid.org/0000-0003-2878-1147UNSPECIFIED
Sisodiya, Sanjay M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daly, Mark J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helbig, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lal, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lemke, Johannes R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-180605
DOI: 10.1038/s41588-018-0143-7
Journal or Publication Title: Nature Genet.
Volume: 50
Number: 7
Page Range: S. 1048 - 1056
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
AUTISM SPECTRUM DISORDER; KCNQ2 ENCEPHALOPATHY; INTELLECTUAL DISABILITIES; SEQUENCE VARIANTS; ILAE COMMISSION; MUTATIONS; CLASSIFICATION; PREVALENCE; GUIDELINES; PHENOTYPESMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18060

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