Reference : De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy
Scientific journals : Article
Life sciences : Genetics & genetic processes
Human health sciences : Neurology
http://hdl.handle.net/10993/20305
De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy
English
Syrbe, Steffen []
Hedrich, Ulrike B.S. []
Riesch, Erik []
Djémié, Tanja []
Müller, Stephan []
Møller, Rikke S. []
Maher, Bridget []
Hernandez-Hernandez, Laura []
Synofzik, Matthis []
Caglayan, Hande S. []
Arslan, Mutluay []
Serratosa, José M. []
Nothnagel, Michael []
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Krause, Roland mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Löffler, Heidrun []
Detert, Katja []
Dorn, Thomas []
Vogt, Heinrich []
Krämer, Günter []
Schöls, Ludger []
Mullis, Primus E. []
Linnankivi, Tarja []
Lehesjoki, Anna-Elina []
Sterbova, Katalin []
Craiu, Dana C. []
Hoffman-Zacharska, Dorota []
Korff, Christian M. []
Weber, Yvonne G. []
Steinlin, Maja []
Gallati, Sabina []
Bertsche, Astrid []
Bernhard, Matthias K. []
Merkenschlager, Andreas []
Kiess, Wieland []
EUROEPINOMICS RES consortium []
Balling, Rudi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Gonzalez, Michael []
Züchner, Stefan []
Palotie, Aarno []
Suls, Arvid []
De Jonghe, Peter []
Helbig, Ingo []
Biskup, Saskia []
Wolff, Markus []
Maljeviv, Snezana []
Schüle, Rebecca []
Sisodoya, Sanjay M. []
Weckhuysen, Sarah []
Lerche, Holger []
Lemke, Johannes R. []
9-Mar-2015
Nature Genetics
Nature Publishing Group
47
4
393-9
Yes (verified by ORBilu)
International
1061-4036
1546-1718
New York
NY
[en] Genetics ; Epilepsy ; Mutation
[en] Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features1–6. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the
potassium channel KV1.2, in six patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons.
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group)
Researchers ; Professionals
http://hdl.handle.net/10993/20305
10.1038/ng.3239
http://www.nature.com/ng/journal/v47/n4/full/ng.3239.html

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Limited access
NG.3239_Proof.pdfAuthor preprint1 MBRequest a copy

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.