Unusual Voltage-Gated Sodium and Potassium Channelopathies Related to Epilepsy.

IF 2.9 3区医学 Q2 CLINICAL NEUROLOGY

Journal of Clinical Neurology Pub Date : 2024-07-01 DOI:10.3988/jcn.2023.0435

Hui Jin Shin, Ara Ko, Se Hee Kim, Joon Soo Lee, Hoon-Chul Kang

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引用次数: 0

Abstract

Background and purpose: There is extensive literature on monogenic epilepsies caused by mutations in familiar channelopathy genes such as SCN1A. However, information on other less-common channelopathy genes is scarce. This study aimed to explore the genetic and clinical characteristics of patients diagnosed with unusual voltage-gated sodium and potassium channelopathies related to epilepsy.

Methods: This observational, retrospective study analyzed pediatric patients with epilepsy who carried pathogenic variants of unusual voltage-gated sodium and potassium channelopathy genes responsible for seizure-associated phenotypes. Targeted next-generation sequencing (NGS) panel tests were performed between November 2016 and June 2022 at Severance Children's Hospital, Seoul, South Korea. Clinical characteristics and the treatment responses to different types of antiseizure medications were further analyzed according to different types of gene mutation.

Results: This study included 15 patients with the following unusual voltage-gated sodium and potassium channelopathy genes: SCN3A (n=1), SCN4A (n=1), KCNA1 (n=1), KCNA2 (n=4), KCNB1 (n=6), KCNC1 (n=1), and KCNMA1 (n=1). NGS-based genetic testing identified 13 missense mutations (87%), 1 splice-site variant (7%), and 1 copy-number variant (7%). Developmental and epileptic encephalopathy was diagnosed in nine (60%) patients. Seizure freedom was eventually achieved in eight (53%) patients, whereas seizures persisted in seven (47%) patients.

Conclusions: Our findings broaden the genotypic and phenotypic spectra of less-common voltage-gated sodium and potassium channelopathies associated with epilepsy.

查看原文本刊更多论文

与癫痫有关的异常电压门控钠和钾通道病。

背景和目的：关于由 SCN1A 等熟悉的通道病变基因突变引起的单基因癫痫的文献很多。然而，有关其他不太常见的通道病变基因的资料却很少。本研究旨在探讨被诊断为与癫痫相关的不常见电压门钠离子和钾离子通道病变患者的遗传和临床特征：这项观察性、回顾性研究分析了携带导致癫痫发作相关表型的异常电压门控钠和钾通道病变基因致病变体的儿科癫痫患者。2016年11月至2022年6月期间，在韩国首尔Severance儿童医院进行了有针对性的新一代测序（NGS）面板测试。根据不同类型的基因突变进一步分析了临床特征和对不同类型抗癫痫药物的治疗反应：本研究共纳入了15名具有以下异常电压门控钠钾通道病基因的患者：SCN3A（n=1）、SCN4A（n=1）、KCNA1（n=1）、KCNA2（n=4）、KCNB1（n=6）、KCNC1（n=1）和KCNMA1（n=1）。基于 NGS 的基因检测发现了 13 个错义突变（87%）、1 个剪接位点变异（7%）和 1 个拷贝数变异（7%）。九名患者（60%）被诊断为发育性和癫痫性脑病。8名患者（53%）最终摆脱了癫痫发作，而7名患者（47%）的癫痫发作仍在持续：我们的研究结果拓宽了与癫痫相关的不常见电压门控钠钾通道病的基因型和表型谱。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Neurology 医学-临床神经学

CiteScore

4.50

自引率

6.50%

发文量

审稿时长

>12 weeks

期刊介绍： The JCN aims to publish the cutting-edge research from around the world. The JCN covers clinical and translational research for physicians and researchers in the field of neurology. Encompassing the entire neurological diseases, our main focus is on the common disorders including stroke, epilepsy, Parkinson''s disease, dementia, multiple sclerosis, headache, and peripheral neuropathy. Any authors affiliated with an accredited biomedical institution may submit manuscripts of original articles, review articles, and letters to the editor. The JCN will allow clinical neurologists to enrich their knowledge of patient management, education, and clinical or experimental research, and hence their professionalism.