Reference : Heterozygous variants in KCNC2 cause a broad spectrum of epilepsy phenotypes associat...
E-prints/Working papers : Already available on another site
Life sciences : Genetics & genetic processes
Human health sciences : Neurology
Systems Biomedicine
http://hdl.handle.net/10993/47272
Heterozygous variants in KCNC2 cause a broad spectrum of epilepsy phenotypes associated with characteristic functional alterations 2021.05.21.21257099
English
Schwarz, Niklas [> >]
Seiffert, Simone [> >]
Pendziwiat, Manuela [> >]
Rademacher, Annika [> >]
Brünger, 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, Lejla [> >]
Oegema, Renske [> >]
Ortal, Barel [> >]
Papacostas, Savvas S. [> >]
Ragona, Francesca [> >]
Granata, Tiziana [> >]
Reif, Philipp S. [> >]
Rosenow, Felix [> >]
Rothschild, Annick [> >]
Scudieri, Paolo [> >]
Striano, Pasquale [> >]
Tinuper, Paolo [> >]
Tanteles, George A. [> >]
Vetro, Annalisa [> >]
Zahnert, Felix [> >]
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-May-2021
Cold Spring Harbor Laboratory Press
No
[en] KCNC2 ; epilepsy ; potassium channel
[en] Background KCNC2 encodes a member of the shaw-related voltage-gated potassium channel family (KV3.2), which are important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain.Methods Individuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic and functional analysis. The cases were referred through clinical and research collaborations in our study. Four de novo variants were examined electrophysiologically in Xenopus laevis oocytes.Results We identified novel KCNC2 variants in 27 patients with various forms of epilepsy. Functional analysis demonstrated gain-of-function in severe and loss-of-function in milder phenotypes as the underlying pathomechanisms with specific response to valproic acid.Conclusion These findings implicate KCNC2 as a novel causative gene for epilepsy emphasizing the critical role of KV3.2 in the regulation of brain excitability with an interesting genotype-phenotype correlation and a potential concept for precision medicine.
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
BMBF Treat-ION grant (01GM1907).
Researchers ; Professionals
http://hdl.handle.net/10993/47272
10.1101/2021.05.21.21257099
https://www.medrxiv.org/content/early/2021/05/23/2021.05.21.21257099
https://www.medrxiv.org/content/10.1101/2021.05.21.21257099v1
FnR ; FNR11583046 > Roland Krause > MechEPI > Epileptogenesis Of Genetic Epilepsies > 01/04/2018 > 31/03/2021 > 2017

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