广东地区新生儿葡萄糖-6-磷酸脱氢酶缺乏症常见基因突变位点的研究

摘要

Objective To investigate the genotypic frequency of glucose-6-phosphate dehydrogenase (G6PD) (1376G ＞ T),G6PD 1311C ＞ T and G6PD IVS11-93T ＞ C in 50 newborns with G6PD deficiency in Guangdong region.Methods To identify G6PD deficiency in the patients of neonatal ward in Guangzhou First People's Hospital during 2010,detected by methemoglobin reduction test and measurement of G6PD/6-phosphate dehydrogenase (6PGD) ratio.Fifty G6PD deficiency subjects were classified into the experimental group,20 neonatal jaundice subjects were classified into the control group.Genomic DNA was extracted by standard method from the peripheral blood of each subject.PCR-direct DNA sequence analysis was used to identify G6PD 1376G ＞ T,1311C ＞ T and 11 intron 93T ＞ C mutations.Results The overall results of mutation analysis in the 50 G6PD deficiency subjects showed the existence of 3 different alleles:G6PD 1376G ＞T,1311C ＞T,11 intron 93T ＞ C(including 1311C ＞ T/IVS11-93T ＞ C and 1376G ＞T/1311C ＞T/IVS11-93T ＞ C complex mutations).The different genotypic frequency in the experimental group was G6PD 1376G ＞T 26.0％ (13/50 cases),1311C ＞ T 4.0％ (2/50 cases),11 intron 93T ＞ C 4.0％ (2/50 cases),1311C ＞ T/IVS11-93T ＞ C 2.0％ (1/50 cases),1376G ＞ T/1311C ＞ T/IVS11-93T ＞ C 2.0％ (1/50 cases).The G6PD enzyme activity of the subjects with 1311C ＞ T/IVS11-93T ＞ C and 1376G ＞ T/1311C ＞ T/IVS11-93T ＞ C complex mutation were reduced.These G6PD mutations were not found in the controls.Conclusions G6PD 1376G ＞ T is one of the commonest mutation in G6PD deficiency newborn in Guangdong region.A novel complex mutation 1376G ＞ T/1311C ＞ T/IVS11-93T ＞ C in this study was found.%目的 了解广东地区新生儿葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症患儿G6PD基因常见突变类型G6PD(1376G＞T),以及2种少见突变类型1311C＞T和11内含子93 T＞C的发生情况.方法 选择2010年广州市第一人民医院新生儿科患者以高铁血红蛋白(MetHb)还原率及G6PD/6-磷酸葡萄糖酸脱氢酶比值法诊断G6PD缺乏症,选择50例广东籍G6PD缺乏症新生儿为试验组,20例黄疸新生儿为对照组,提取2组患儿外周静脉血基因组DNA,应用PCR-DNA直接测序法检测G6PD 1376G＞T、1311C＞T和11内含子93 T＞C突变类型.结果 试验组检测出G6PD基因突变类型3种:1376G＞T、1311C ＞T和11内含子93T＞C.50例试验组标本中,检测出1376G＞T突变类型13例(26.0％),1311C＞T 2例(4.0％)、11内含子93T＞C 2例(4.0％).其中1311C＞ T/IVS11-93T＞C复合突变1例,存在1376G＞ T/1311C＞ T/IVS11-93T＞C复合突变1例,1311C＞ T/IVS11-93T＞C和1376G＞ T/1311C＞ T/IVS11-93T＞C复合突变的病例G6PD酶活性均降低.对照组未检出G6PD基因突变.结论 1376G＞T是广东地区新生儿G6PD缺乏症人群中最常见的G6PD基因突变类型之一;同时发现G6PD基因1376G＞T/1311C＞ T/IVS11-93T＞C出现复合突变.