Seiffert Simone, Pendziwiat Manuela, Hedrich Ulrike B S, Helbig Ingo, Weber Yvonne, Schwarz Niklas
Department of Human Genetics, University Hospital Ulm, Ulm, Germany.
Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Front Neurol. 2023 Jun 9;14:1212079. doi: 10.3389/fneur.2023.1212079. eCollection 2023.
Recently, variants in , coding for the potassium channel subunit K3.2, have been described as causative for various forms of epilepsy including genetic generalized epilepsy (GGE) and developmental and epileptic encephalopathy (DEE). Here, we report the functional characteristics of three additional variants of uncertain significance and one variant classified as pathogenic. Electrophysiological studies were performed in oocytes. The data presented here support that variants with uncertain significance may also be causative for various forms of epilepsy, as they show changes in the current amplitude and activation and deactivation kinetics of the channel, depending on the variant. In addition, we investigated the effect of valproic acid on K3.2, as several patients carrying pathogenic variants in the gene achieved significant seizure reduction or seizure freedom with this drug. However, in our electrophysiological investigations, no change on the behavior of K3.2 channels could be observed, suggesting that the therapeutic effect of VPA may be explained by other mechanisms.
最近，编码钾通道亚基K3.2的基因中的变异已被描述为导致各种形式癫痫的原因，包括遗传性全身性癫痫（GGE）和发育性癫痫性脑病（DEE）。在此，我们报告另外三个意义未明的变异以及一个被分类为致病性变异的功能特征。在卵母细胞中进行了电生理研究。此处呈现的数据支持，意义未明的变异也可能导致各种形式的癫痫，因为它们会根据变异情况使通道的电流幅度、激活和失活动力学发生变化。此外，我们研究了丙戊酸对K3.2的影响，因为几名携带该基因致病性变异的患者使用这种药物后癫痫发作显著减少或不再发作。然而，在我们的电生理研究中，未观察到K3.2通道行为的变化，这表明丙戊酸的治疗效果可能由其他机制解释。
