Reference : Clinical spectrum of STX1B-related epileptic disorders
Scientific journals : Article
Life sciences : Genetics & genetic processes
Human health sciences : Neurology
Systems Biomedicine
http://hdl.handle.net/10993/36676
Clinical spectrum of STX1B-related epileptic disorders
English
Wolking, Stefan []
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Mei, Davide []
Møller, Rikke S. []
Balestrini, Simona []
Helbig, Katherine L. []
Altuzurra, Cecilia D. []
Chatron, Nicolas []
Kaiwar, Charu []
Stöhr, Katharina []
Widdess-Walsh, Peter []
Mendelsohn, Bryce A. []
Numis, Adam []
Cilio, Maria R. []
Van Paesschen, Wim []
Svendsen, Lene L. []
Oates, Stephanie []
Hughes, Elaine []
Goyal, Sushma []
Brown, Kathleen []
Sifuentes Saenz []
Dorn, Thomas []
Muhle, Hiltrud []
Pagnamenta, Alistair T. []
Vavoulis, Dimitris V. []
Knight, Samantha J.L. []
Taylor, Jenny C. []
Canevini, Maria P. []
Darra, Franchesca []
Gavrilova, Ralitza H. []
Powis, Zöe []
Tang, Shan []
Marquetand, Justus []
Armstrong, Martin []
McHale, Duncan []
Klee, Ernst W. []
Kluger, Gerhard J. []
Lowenstein, Daniel H. []
Weckhuysen, Sarah []
Pal, Deb K. []
Helbig, Ingo []
Guerrini, Renzo []
Thomas, Rhys H. []
Rees, Mark I. []
Lesca, Gaetan []
Sisodiya, Sanjay M. []
Weber, Yvonne G. []
Lal, Dennis []
Marini, Carla []
Lerche, Holger []
Schubert, Julian []
8-Feb-2019
Neurology
Lippincott Williams & Wilkins
92
1-12
Yes (verified by ORBilu)
International
0028-3878
1526-632X
Hagerstown
MD
[en] epilepsy ; seizures ; STX1B
[en] Objective: The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and to establish genotype-phenotype correlations by identifying further disease-related variants.
Methods: We used next generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases. To estimate the pathogenicity of the variants, we used established and newly developed in silico prediction tools.
Results: We describe fifteen new variants in STX1B which are distributed across the whole gene. We discerned four different phenotypic groups across the newly identified and previously published patients (49 in 23 families): 1) Six sporadic patients or families (31 affected individuals) with febrile and afebrile seizures with a benign course, generally good drug response, normal development and without permanent neurological deficits; 2) two patients of genetic generalized epilepsy without febrile seizures and cognitive deficits; 3) thirteen patients or families with intractable seizures, developmental regression after seizure onset and additional neuropsychiatric symptoms; 4) two patients with focal epilepsy. Nonsense mutations were found more often in benign syndromes, whereas missense variants in the SNARE motif of syntaxin-1B were associated with more severe phenotypes.
Conclusion: These data expand the genetic and phenotypic spectrum of STX1B-related epilepsies to a diverse range of epilepsies that span the ILAE classification. Variants in STX1B are protean, and able to contribute to many different epilepsy phenotypes, similar to SCN1A, the most important gene associated with fever-associated epilepsies.
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Researchers
http://hdl.handle.net/10993/36676
10.1212/WNL.0000000000007089
http://n.neurology.org/content/early/2019/02/08/WNL.0000000000007089

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