| Autor: |
Manuela Pendziwiat, Renske Oegema, Ioanna Kousiappa, Yvonne G. Weber, Francesca Ragona, Dennis Lal, Ulrike B. S. Hedrich, Mulahasanovic L, Gali Heimer, Kearney H, Hiltrud Muhle, Pasquale Striano, Paolo Scudieri, Annika Rademacher, Rothschild A, Michele Iacomino, Lohmann E, Augustijn Pb, Russell J. Buono, Holger Lerche, Philipp S. Reif, George A. Tanteles, Karl Martin Klein, Bayat A, Francesca Bisulli, Wolfram S. Kunz, Montgomery S, Bruria Bz, Papacostas Ss, Renzo Guerrini, Laura Licchetta, Ingo Helbig, Bruenger T, Federico Zara, Zahnert F, Marie T. McDonald, Hartmut Baier, Patrick May, Niklas Schwarz, Doyle Mg, Simone Seiffert, Vetro A, Paolo Tinuper, Ortal B, Tiziana Granata, Felix Rosenow, Raffaella Minardi |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
BackgroundKCNC2 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.MethodsIndividuals 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.ResultsWe 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.ConclusionThese 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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