Novel KCNQ3 muation in a large family with benign familial neonatal epilepsy

• Verfasst von: Maljevic, Snezana [VerfasserIn]
• Verfasst von: Vejzovic, Sabina [VerfasserIn]
• Verfasst von: Bernhard, Matthias K. [VerfasserIn]
• Verfasst von: Bertsche, Astrid [VerfasserIn]
• Verfasst von: Weise, Sebastian [VerfasserIn]
• Verfasst von: Döcker, Miriam [VerfasserIn]
• Verfasst von: Lerche, Holger [VerfasserIn]
• Verfasst von: Lemke, Johannes R. [VerfasserIn]
• Verfasst von: Merkenschlager, Andreas [VerfasserIn]
• Verfasst von: Syrbe, Steffen [VerfasserIn]
• Titel: Novel KCNQ3 muation in a large family with benign familial neonatal epilepsy
• Titelzusatz: a rare cause of neonatal seizures
• Verf.angabe: Snezana Maljevic, Sabina Vejzovic, Matthias K. Bernhard, Astrid Bertsche, Sebastian Weise, Miriam Döcker, Holger Lerche, Johannes R. Lemke, Andreas Merkenschlager, Steffen Syrbe
• E-Jahr: 2016
• Jahr: July 7, 2016
• Umfang: 8 S.
• Fussnoten: Gesehen am 06.05.2020
• Titel Quelle: Enthalten in: Molecular syndromology
• Ort Quelle: Basel : Karger, 2010
• Jahr Quelle: 2016
• Band/Heft Quelle: 7(2016), 4, Seite 189-196
• ISSN Quelle: 1661-8777
• DOI: doi:10.1159/000447461
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1697296505

Abstract

Benign familial neonatal seizures (BFNS) present a rare familial epilepsy syndrome caused by genetic alterations in the voltage-gated potassium channels Kv7.2 and Kv7.3, encoded by <i>KCNQ2</i> and <i>KCNQ3.</i> While most BFNS families carry alterations in <i>KCNQ2</i>, mutations in <i>KCNQ3</i> appear to be less common. Here, we describe a family with 6 individuals presenting with neonatal focal and generalized seizures. Genetic testing revealed a novel <i>KCNQ3</i> variant, c.835G>T, cosegregating with seizures in 4 tested individuals. This variant results in a substitution of the highly conserved amino acid valine localized within the pore-forming transmembrane segment S5 (p.V279F). Functional investigations in <i>Xenopus laevis</i> oocytes revealed a loss of function, which supports p.V279F as a pathogenic mutation. When p.V279F was coexpressed with the wild-type (WT) Kv7.2 subunits, the resulting potassium currents were about 10-fold reduced compared to the WT Kv7.3 and Kv7.2 coexpression. Genotype-phenotype correlation shows an incomplete penetrance of p.V279F. Response to antiepileptic treatment was variable, but evaluation of treatment response remained challenging due to the self-limiting character of the disease. The identification of the pathogenic variant helped to avoid unnecessary investigations in affected family members and allowed guided therapy.