Reference : Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy s...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Human health sciences : Neurology
http://hdl.handle.net/10993/18655
Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes
English
Schubert, Julian [> >]
Siekierska, Aleksandra [> >]
Langlois, Melanie mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Huneau, Clement [> >]
Becker, Felicitas [> >]
Muhle, Hiltrud [> >]
Suls, Arvid [> >]
Lemke, Johannes R. [> >]
de Kovel, Carolien G. F. [> >]
Thiele, Holger [> >]
Konrad, Kathryn [> >]
Kawalia, Amit [> >]
Toliat, Mohammad R. [> >]
Sander, Thomas [> >]
Ruschendorf, Franz [> >]
Caliebe, Almuth [> >]
Nagel, Inga [> >]
Kohl, Bernard [> >]
Kecskes, Angela [> >]
Jacmin, Maxime mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Hardies, Katia [> >]
Weckhuysen, Sarah [> >]
Riesch, Erik [> >]
Dorn, Thomas [> >]
Brilstra, Eva H. [> >]
Baulac, Stephanie [> >]
Moller, Rikke S. [> >]
Hjalgrim, Helle [> >]
Koeleman, Bobby P. C. [> >]
EuroEPINOMICS RES Consortium [> >]
Krause, Roland mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Jurkat-Rott, Karin [> >]
Lehman-Horn, Frank [> >]
Roach, Jared C. [> >]
Glusman, Gustavo [> >]
Hood, Leroy [> >]
Galas, David J. [> >]
Martin, Benoit [> >]
de Witte, Peter A. M. [> >]
Biskup, Saskia [> >]
De Jonghe, Peter [> >]
Helbig, Ingo [> >]
Balling, Rudi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Nurnberg, Peter [> >]
Crawford, Alexander Dettmar mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Esguerra, Camila V. [> >]
Weber, Yvonne G. [> >]
Lerche, Holger [> >]
2-Nov-2014
Nature Genetics
Nature Publishing Group
46
12
1327-32
Yes (verified by ORBilu)
International
1061-4036
1546-1718
New York
NY
[en] Febrile seizures affect 2–4% of all children1 and have a strong genetic component2. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)3, 4, 5 have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B6, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees7, 8 identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes.
Luxembourg Centre for Systems Biomedicine (LCSB): Chemical Biology (Crawford Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group)
Researchers
http://hdl.handle.net/10993/18655
10.1038/ng.3130
http://dx.doi.org/10.1038/ng.3130

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