Reference : Spectrum of Phenotypic, Genetic, and Functional Characteristics in Epilepsy Patients ...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Human health sciences : Neurology
Systems Biomedicine
http://hdl.handle.net/10993/50656
Spectrum of Phenotypic, Genetic, and Functional Characteristics in Epilepsy Patients With KCNC2 Pathogenic Variants 10.1212/WNL.0000000000200660
English
Schwarz, Niklas [> >]
Seiffert, Simone [> >]
Pendziwiat, Manuela [> >]
Rademacher, Annika Verena [> >]
BrÃ\textonequarternger, Tobias [> >]
Hedrich, Ulrike B. S. [> >]
Augustijn, Paul B. [> >]
Baier, Hartmut [> >]
Bayat, Allan [> >]
Bisulli, Francesca [> >]
Buono, Russell J. [> >]
Bruria, Ben Zeev [> >]
Doyle, Michael G. [> >]
Guerrini, Renzo [> >]
Heimer, Gali [> >]
Iacomino, Michele [> >]
Kearney, Hugh [> >]
Klein, Karl Martin [> >]
Kousiappa, Ioanna [> >]
Kunz, Wolfram S. [> >]
Lerche, Holger [> >]
Licchetta, Laura [> >]
Lohmann, Ebba [> >]
Minardi, Raffaella [> >]
McDonald, Marie [> >]
Montgomery, Sarah [> >]
Mulahasanovic, Leijla [> >]
Oegema, Renske [> >]
Ortal, Barel [> >]
Papacostas, Savvas S. [> >]
Ragona, Francesca [> >]
Granata, Tiziana [> >]
Reif, Phillip S. [> >]
Rosenow, Felix [> >]
Rothschild, Annick [> >]
Scudieri, Paolo [> >]
Striano, Pasquale [> >]
Tinuper, Paolo [> >]
Tanteles, George A. [> >]
Vetro, Annalisa [> >]
Zahnert, Felix [> >]
Goldberg, Ethan M. [> >]
Zara, Federico [> >]
Lal, Dennis [> >]
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core]
Muhle, Hiltrud [> >]
Helbig, Ingo [> >]
Weber, Yvonne [> >]
21-Mar-2022
Neurology
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Yes (verified by ORBilu)
International
0028-3878
[en] KCNC2 ; epilepsy ; Kv3.2
[en] Background: KCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. The objective of this study was to analyse the clinical phenotype, genetic background, and biophysical function of disease-associated Kv3.2 variants.Methods: Individuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic, and functional analysis. Cases were referred through clinical and research collaborations. Selected de novo variants were examined electrophysiologically in Xenopus laevis oocytes.Results: We identified novel KCNC2 variants in 18 patients with various forms of epilepsy including genetic generalized epilepsy (GGE), developmental and epileptic encephalopathy (DEE) including early-onset absence epilepsy (EOAE), focal epilepsy (FE), and myoclonic-atonic epilepsy (MAE). 10/18 variants were de novo and 8/18 variants were classified as modifying variants. 8 drug responsive cases became seizure-free using valproic acid as monotherapy or in combination including severe DEE cases. Functional analysis of four variants demonstrated gain-of-function in three severely affected DEE cases and loss-of-function in one case with a milder phenotype (GGE) as the underlying pathomechanisms.Conclusion: These findings implicate KCNC2 as a novel causative gene for epilepsy and emphasize the critical role of KV3.2 in the regulation of brain excitability.
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Fonds National de la Recherche - FnR
TreatIon
Researchers ; Professionals
http://hdl.handle.net/10993/50656
10.1212/WNL.0000000000200660
https://n.neurology.org/content/early/2022/03/21/WNL.0000000000200660
FnR ; FNR11583046 > Roland Krause > MechEPI > Epileptogenesis Of Genetic Epilepsies > 01/04/2018 > 30/06/2021 > 2017

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