<italic style="font-style: italic">POLG </italic>Mutations Are Probably Rare in the Han Chinese Population

Yang Kunfang; Meng Linyi; Zhang Yuanfeng; Yang Yongchen; Cheng Hongyi; Jiang Zhihu; Zhang Hong; Chen Yucai

doi:10.24920/003697

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POLG Mutations Are Probably Rare in the Han Chinese Population

Chinese Medical Sciences Journal Vol. 35, Issue 4, Pages: 350-356(2020)

Original Article | Updated：2024-04-10

- POLG Mutations Are Probably Rare in the Han Chinese Population
- Affiliations：
  
  1. 1Department of Neurology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
  2. 2Department of Pharmacy, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
  3. 3Clinical Laboratory, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
- Author bio：
  
  * E-mail: chenyc@shchildren.com.cn; Tel: 86-21-62474880.
- Funds：
- DOI：10.24920/003697
  CLC：
- Received：13 December 2019，
  
  Accepted：2020-5-12，
  
  Published Online：31 December 2020，
  
  Published：31 December 2020
- Accepted：
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Yang Kunfang, Meng Linyi, Zhang Yuanfeng, et al. POLG Mutations Are Probably Rare in the Han Chinese Population[J]. Chinese medical sciences journal, 2020, 35(4): 350-356.
DOI：

Yang Kunfang, Meng Linyi, Zhang Yuanfeng, et al. POLG Mutations Are Probably Rare in the Han Chinese Population[J]. Chinese medical sciences journal, 2020, 35(4): 350-356. DOI： 10.24920/003697.

摘要

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。

Abstract

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.

关键词

Keywords

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⁰

POLG Mutations Are Probably Rare in the Han Chinese Population

DOI：10.24920/003697

摘要

Abstract

关键词

Keywords

references