Zheng Yiting, Chen Jing
Department of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Front Neurol. 2024 Oct 7;15:1466075. doi: 10.3389/fneur.2024.1466075. eCollection 2024.
Recent advances in exome and targeted sequencing have significantly improved the aetiological diagnosis of epilepsy, revealing an increasing number of epilepsy-related pathogenic genes. As a result, the diagnosis and treatment of epilepsy have become more accessible and more traceable. Voltage-gated potassium channels (Kv) regulate electrical excitability in neuron systems. Mutate Kv channels have been implicated in epilepsy as demonstrated in case reports and researches using gene-knockout mouse models. Both gain and loss-of-function of Kv channels lead to epilepsy with similar phenotypes through different mechanisms, bringing new challenges to the diagnosis and treatment of epilepsy. Research on genetic epilepsy is progressing rapidly, with several drug candidates targeting mutated genes or channels emerging. This article provides a brief overview of the symptoms and pathogenesis of epilepsy associated with voltage-gated potassium ion channels dysfunction and highlights recent progress in treatments. Here, we reviewed case reports of gene mutations related to epilepsy in recent years and summarized the proportion of Kv genes. Our focus is on the progress in precise treatments for specific voltage-gated potassium channel genes linked to epilepsy, including KCNA1, KCNA2, KCNB1, KCNC1, KCND2, KCNQ2, KCNQ3, KCNH1, and KCNH5.
外显子组测序和靶向测序的最新进展显著改善了癫痫的病因诊断，揭示了越来越多与癫痫相关的致病基因。因此，癫痫的诊断和治疗变得更易实现且更具可追溯性。电压门控钾通道（Kv）调节神经元系统中的电兴奋性。如病例报告和使用基因敲除小鼠模型的研究所表明，Kv通道突变与癫痫有关。Kv通道的功能获得和功能丧失均通过不同机制导致具有相似表型的癫痫，给癫痫的诊断和治疗带来了新的挑战。遗传性癫痫的研究进展迅速，出现了几种针对突变基因或通道的候选药物。本文简要概述了与电压门控钾离子通道功能障碍相关的癫痫的症状和发病机制，并重点介绍了治疗方面的最新进展。在此，我们回顾了近年来与癫痫相关的基因突变的病例报告，并总结了Kv基因的比例。我们关注的是与癫痫相关的特定电压门控钾通道基因精确治疗的进展，包括KCNA1、KCNA2、KCNB1、KCNC1、KCND2、KCNQ2、KCNQ3、KCNH1和KCNH5。
