G6PD基因非热点突变基因诊断  

Diagnosis of G6PD gene non-hot spot mutation

作　　者：古艳 方颖慧 刘媛 徐丹丹 徐细花 李丽萍 GU Yan;FANG Yinghui;LIU Yuan;XU Dandan;XU Xihua;LI Liping(Department of Clinical Laboratory,Nanchang First Hospital,Nanchang 330006,China;Department of Pediatrics,Nanchang First Hospital,Nanchang 330006,China.)

机构地区：[1]南昌市第一医院检验科,江西南昌330006 [2]南昌市第一医院儿科,江西南昌330006

出　　处：《实验与检验医学》2024年第3期221-224,229,共5页Experimental and Laboratory Medicine

基　　金：国家自然科学基金项目,编号81602554。

摘　　要：目的分析3例(其中2例常见12个热点突变检测结果呈阴性)葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症患儿及母亲的G6PD基因,明确G6PD基因突变情况,为用药和饮食指导提供分子依据。方法采集外周血提取DNA,用DNA双脱氧链终止法(Sanger)测序技术对3例患儿G6PD基因编码区进行检测,继而对患儿母亲行相应点突变检测。查询常用人类基因突变数据库(HGMD)、突变数据库Mutation、ClinVar等分析检测结果,并根据美国医学遗传学和基因组学学会(ACMG)制定的遗传变异分类标准与指南,对基因突变结果进行致病性评级。结果检测出3个患儿分别为G6PD基因c.208T>C半合子突变、c.440A>G半合子突变、c.1376G>T半合子突变,3位母亲相应位点均呈杂合突变。G6PD基因c.440A>G突变在常用突变数据库HGMD和ClinVar未见收录报告,可能为新发突变。根据ACMG遗传变异分类标准与指南,将检测到的3个患者G6PD基因c.1376G>T、c.208T>C及c.440A>G突变分别评级为致病突变、可能致病突变及意义不明。结论对G6PD基因常见热点突变检测呈阴性结果的G6PD缺乏症患者,可用Sanger测序技术检测其G6PD基因编码区,查明基因突变情况,这有助于临床用药治疗及饮食指导。Objective To analyze the G6PD gene of three children with G6PD deficiency and their mothers,and to provide molecular basis for medication and diet guidance.Methods DNA was extracted from peripheral venous blood,and the coding region of G6PD gene was detected by Sanger sequencing technology in 3 patients,and then the corresponding point mutation was detected in their mothers.The detection results were compared with the information of Human Gene Mutation databases such as HGMD,Mutation Database and ClinVar.According to the classification criteria and guidelines of genetic variants developed by ACMG,the gene mutation results were rated for pathogenicity.Results Three children were detected as G6PD gene C.208T>C hemizygous mutation,c.440A>G hemizygous mutation,c.1376G>T hemizygous mutation,respectively.Their mother were happened corresponding heterozygous mutations.The C.440A>G mutation of G6PD gene was not reported in the database of HGMD and ClinVar,which may be a novel mutation.According to the classification criteria and guidelines of genetic variants developed by ACMG,the G6PD gene mutations c.1376G>T,c.208T>C and c.440A>G detected in three patients were classified as pathogenic,possible pathogenic and uncertain significance,respectively.Conclusions Sanger sequencing technology can be used to detect the coding region of G6PD gene in G6PD deficiency patients,who with negative results of hotspot mutations.Identifying gene mutation is helpful for clinical medication treatment and diet guidance.

关 键 词：G6PD缺乏症 Sanger测序 非热点突变 基因诊断 

分 类 号：R722.1[医药卫生—儿科]