Department of Neurology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China.
Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China.
Chin Med Sci J. 2020 Dec 31;35(4):350-356. doi: 10.24920/003697.
Objective Mutations in polymerase gamma gene ( are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy. The aim of this study is to investigate the incidence/prevalence of pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid (VPA) exposure at Shanghai Children's Hospital were collected from 2015 to 2019. The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy (ILAE). Blood sampling were performed before VPA treatment. The gene DNA was sequenced by either the first or the next generation sequencing (NGS). The variant burden was illustrated. Liver functions were tested to describe whether they experienced VPA toxicity.Results Totally 216 Han Chinese patients were included, aged from 1 month to 15 years old, 102 were male and 114 were female. The onset age was 1 month old to 13 years old, and the epilepsy course ranged from 2 weeks to about 3 years. VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage. No patient experienced hepatic toxicity following VPA exposure. DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of . Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients, and single heterozygous mutation of c.156_158dupGCA was found in 1 patient. None of these variants showed clinical significance.Conclusions Functional modifying homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study. mutation frequency might be rare in Han Chinese, and standard VPA therapeutic dosage might be safe for Han Chinese patients.
目的
聚合酶γ基因（的突变被认为是导致早发性和少年起病的非综合征性难治性癫痫的重要原因。本研究旨在通过测序探讨汉族癫痫患者中致病性变异的发生率/患病率。
方法
收集 2015 年至 2019 年在上海儿童医学中心就诊的暴露于丙戊酸（VPA）前的癫痫汉族患者。临床诊断基于国际抗癫痫联盟（ILAE）2014 年癫痫共识声明。在 VPA 治疗前进行血样采集。通过第一代或下一代测序（NGS）对基因 DNA 进行测序。描述了变异负担。检测肝功能以描述他们是否经历过 VPA 毒性。
结果
共纳入 216 例汉族患者，年龄 1 个月至 15 岁，男 102 例，女 114 例。发病年龄为 1 个月至 13 岁，癫痫病程 2 周至约 3 年。VPA 以标准剂量治疗全面性或难治性部分性发作。VPA 暴露后无患者出现肝毒性。DNA 测序数据显示，无患者存在或复合杂合突变。在 2 例患者中发现了 c.1150G>T 和 p.D384Y 的单杂合突变，在 1 例患者中发现了 c.156_158dupGCA 的单杂合突变。这些变异均无临床意义。
结论
在本研究中未检测到功能修饰的纯合突变和复合杂合突变，VPA 毒性也未出现。汉族人群中可能存在突变频率较低，标准 VPA 治疗剂量对汉族患者可能是安全的。
