Schubert, Julian, Siekierska, Aleksandra ORCID: 0000-0003-4907-605X, Langlois, Melanie, May, Patrick ORCID: 0000-0001-8698-3770, Huneau, Clement, Becker, Felicitas, Muhle, Hiltrud, Suls, Arvid ORCID: 0000-0003-0328-198X, Lemke, Johannes R., de Kovel, Carolien G. F., Thiele, Holger, Konrad, Kathryn, Kawalia, Amit, Toliat, Mohammad R., Sander, Thomas, Rueschendorf, Franz, Caliebe, Almuth ORCID: 0000-0003-2157-425X, Nagel, Inga, Kohl, Bernard, Kecskes, Angela, Jacmin, Maxime, Hardies, Katia, Weckhuysen, Sarah ORCID: 0000-0003-2878-1147, Riesch, Erik, Dorn, Thomas, Brilstra, Eva H., Baulac, Stephanie ORCID: 0000-0001-6430-4693, Moller, Rikke S., Hjalgrim, Helle, Koeleman, Bobby P. C., Jurkat-Rott, Karin, Lehman-Horn, Frank, Roach, Jared C., Glusman, Gustavo ORCID: 0000-0001-8060-5955, Hood, Leroy, Galas, David J., Martin, Benoit, de Witte, Peter A. M., Biskup, Saskia, De Jonghe, Peter, Helbig, Ingo ORCID: 0000-0001-8486-0558, Balling, Rudi ORCID: 0000-0003-2902-5650, Nuernberg, Peter, Crawford, Alexander D., Esguerra, Camila V., Weber, Yvonne G. and Lerche, Holger (2014). Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes. Nature Genet., 46 (12). S. 1327 - 1333. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

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Abstract

Febrile seizures affect 2-4% of all children(1) and have a strong genetic component(2). Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)(3-5) have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B(6), that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees(7,8) 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schubert, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siekierska, AleksandraUNSPECIFIEDorcid.org/0000-0003-4907-605XUNSPECIFIED
Langlois, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
May, PatrickUNSPECIFIEDorcid.org/0000-0001-8698-3770UNSPECIFIED
Huneau, ClementUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, FelicitasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muhle, HiltrudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suls, ArvidUNSPECIFIEDorcid.org/0000-0003-0328-198XUNSPECIFIED
Lemke, Johannes R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Kovel, Carolien G. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konrad, KathrynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kawalia, AmitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toliat, Mohammad R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rueschendorf, FranzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caliebe, AlmuthUNSPECIFIEDorcid.org/0000-0003-2157-425XUNSPECIFIED
Nagel, IngaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kohl, BernardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kecskes, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jacmin, MaximeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hardies, KatiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weckhuysen, SarahUNSPECIFIEDorcid.org/0000-0003-2878-1147UNSPECIFIED
Riesch, ErikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dorn, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brilstra, Eva H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baulac, StephanieUNSPECIFIEDorcid.org/0000-0001-6430-4693UNSPECIFIED
Moller, Rikke S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hjalgrim, HelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koeleman, Bobby P. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jurkat-Rott, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehman-Horn, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roach, Jared C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glusman, GustavoUNSPECIFIEDorcid.org/0000-0001-8060-5955UNSPECIFIED
Hood, LeroyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galas, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, BenoitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Witte, Peter A. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biskup, SaskiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Jonghe, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helbig, IngoUNSPECIFIEDorcid.org/0000-0001-8486-0558UNSPECIFIED
Balling, RudiUNSPECIFIEDorcid.org/0000-0003-2902-5650UNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Crawford, Alexander D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Esguerra, Camila V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, Yvonne G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lerche, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-422735
DOI: 10.1038/ng.3130
Journal or Publication Title: Nature Genet.
Volume: 46
Number: 12
Page Range: S. 1327 - 1333
Date: 2014
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PAROXYSMAL KINESIGENIC DYSKINESIA; SYNAPTIC VESICLE FUSION; DE-NOVO MUTATIONS; FEBRILE SEIZURES; INFANTILE CONVULSIONS; GENERALIZED EPILEPSY; PRRT2 MUTATIONS; GENERATION; DISORDERS; ZEBRAFISHMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42273

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