中国南方广西壮族自治区葡萄糖-6-磷酸脱氢酶缺乏症的发病率及完整分子特征：四种新突变的描述

Incidence and complete molecular characterization of glucose-6-phosphate dehydrogenase deficiency in the Guangxi Zhuang autonomous region of southern China: description of four novel mutations.

作者信息

Yan Tizhen, Cai Ren, Mo OiuHua, Zhu DongLin, Ouyang Hong, Huang Lihua, Zhao Mingguang, Huang Fen, Li Liyan, Liang Xin, Xu Xiangmin

机构信息

Department of Medical Genetics, Southern Medical University, Tonghe 510515, Guangzhou, Guangdong, PR China.

出版信息

Haematologica. 2006 Oct;91(10):1321-8.

PMID:17018380

Abstract

BACKGROUND AND OBJECTIVES

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human metabolic disorder in southern China. We investigated the incidence and distribution of mutations, the molecular pathology of affected females and the haplotype association with G6PD deficiency in patients from the Guangxi region.

DESIGN AND METHODS

A population-based molecular analysis combining phenotypic screening and genotypic detection using both multiplex primer extension/denaturing high performance liquid chromatography assay and DNA sequence analysis were performed in a total of 4,704 individuals.

RESULTS

The mutation frequency of male G6PD-deficient individuals was observed to be 7.43%. Twenty-seven genotypes from 361 individuals were found. Statistical analysis showed that there were significant differences in both the percentages of methemoglobin and the G6PD/6PGD ratio between heterozygote and hemizygote in males and between heterozygote and homozygote in females. However, no statistically significance was seen between hemizyotes and homozygotes. The mutation profile showed that five mutations, G6PD Kaiping(1388A), G6PD Canton(1376T), G6PD Gaohe(95G), Chinese-5(1024T)and G6PD Viangchan(817A), are the most common in the area, accounting for 85% of the G6PD-deficient alleles. Ten rare mutations were detected in approximately 4% of the mutant chromosomes. Four novel mutations were found: G6PD Liuzhou(442A), G6PD Nanning(703T), G6PD Laibin(1414C,) and G6PD Hechi(202A/817A). In addition, two other rare mutations, c.196T-->A and c.202 G-->A, were detected for the first time in Chinese patients. A single dominant haplotype (- - + - -) was observed in 94.0% of 182 deficient chromosomes.

INTERPRETATION AND CONCLUSIONS

Our protocol could be used to extend the knowledge of molecular defects of G6PD gene in different geographical areas.

摘要

背景与目的

葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症是中国南方最常见的人类代谢紊乱疾病。我们调查了广西地区患者中G6PD突变的发生率和分布情况、受影响女性的分子病理学以及与G6PD缺乏症相关的单倍型。

设计与方法

对总共4704名个体进行了基于人群的分子分析，结合表型筛查和基因型检测，采用多重引物延伸/变性高效液相色谱分析和DNA序列分析。

结果

观察到男性G6PD缺乏个体的突变频率为7.43%。在361名个体中发现了27种基因型。统计分析表明，男性杂合子与半合子之间以及女性杂合子与纯合子之间的高铁血红蛋白百分比和G6PD/6PGD比值均存在显著差异。然而，半合子与纯合子之间未观察到统计学意义。突变谱显示，G6PD开平（1388A）、G6PD广州（1376T）、G6PD高鹤（95G）、中国-5（1024T）和G6PD万象（817A）这五种突变在该地区最为常见，占G6PD缺乏等位基因的85%。在约4%的突变染色体中检测到十种罕见突变。发现了四种新突变：G6PD柳州（442A）、G6PD南宁（703T）、G6PD来宾（1414C）和G6PD河池（202A/817A）。此外，在中国患者中首次检测到另外两种罕见突变c.196T→A和c.202 G→A。在182条缺陷染色体中的94.0%观察到单一优势单倍型（ - - + - -）。