Chinese Medical Sciences Journal ›› 2020, Vol. 35 ›› Issue (4): 350-356.doi: 10.24920/003697

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  1. 1神经内科,上海市儿童医院,上海交通大学,上海 200062,中国
    2药学部,上海市儿童医院,上海交通大学,上海 200062,中国
    3临床检验科,上海市儿童医院,上海交通大学,上海 200062,中国
  • 收稿日期:2019-12-13 接受日期:2020-05-12 出版日期:2020-12-31 发布日期:2021-01-08
  • 通讯作者: 陈育才

POLG Mutations Are Probably Rare in the Han Chinese Population

Kunfang Yang1,Linyi Meng2,Yuanfeng Zhang1,Yongchen Yang3,Hongyi Cheng1,Zhihu Jiang2,Hong Zhang3,Yucai Chen1,*()   

  1. 1Department of Neurology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
    2Department of Pharmacy, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
    3Clinical Laboratory, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
  • Received:2019-12-13 Accepted:2020-05-12 Published:2020-12-31 Online:2021-01-08
  • Contact: Yucai Chen


目的 聚合酶γ基因(ploymerase gamma gene, POLG)突变被认为是儿童和成人早期和青少年发作的非综合征性难治性癫痫的重要原因。本文通过基因测序探讨中国汉族癫痫患者中POLG致病性突变体的发生率/流行率。
方法 选取上海市儿童医院2015-2019年在丙戊酸钠(valproic acid,VPA)暴露前有癫痫发作的中国汉族患者,临床诊断标准基于国际抗癫痫联盟2014年癫痫共识声明。在VPA治疗前采集患者血液样本,采用一代或二代测序(next generation sequencing, NGS)方法对POLG基因进行测序,对POLG变异体进行评估。VPA治疗后随访2-3个月观察患者肝功能变化评价是否出现VPA毒性。
结果 216例中国汉族患者,年龄1个月~15岁,男102例,女114例。癫痫发病年龄1个月~13岁,病程2周~3年左右。由于全面性或顽固性部分性癫痫发作,他们按标准剂量服用VPA。没有患者在服用VPA后出现肝脏毒性。测序数据显示没有患者出现POLG纯合突变或复合杂合子突变。有2例患者检测出有c.1150G>T和p.D384Y单杂合子突变,1例患者有c.156μu_158dupGCA单杂合子突变,均无临床意义。
结论 本研究未发现功能修饰POLG纯合子突变和复合杂合子突变,VPA毒性在本研究中未见。POLG突变频率在汉族人群中可能很少见,VPA治疗剂量对汉族中国人可能相对安全。

关键词: 聚合酶γ, POLG, 癫痫, 丙戊酸, 中国汉族人


Objective Mutations in polymerase gamma gene (POLG) 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 POLG 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 POLG gene DNA was sequenced by either the first or the next generation sequencing (NGS). The POLG 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 POLG. 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 POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study. POLG mutation frequency might be rare in Han Chinese, and standard VPA therapeutic dosage might be safe for Han Chinese patients.

Key words: polymerase gamma, POLG, epilepsy, valproic acid, Han Chinese

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