137例上海地区出生新生儿家系G6PD基因突变分析

Mutation analysis of 137 newborn families with G6PD deficiency in Shanghai

目的了解上海地区出生的新生儿及其家系葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症基因突变特点,探讨该病的发病机制,提高诊断水平。方法用高分辨率熔解曲线分析(HRM)技术对中国人常见的突变类型G1388A、G1376T、A95G、G392T、G871A、C1311T、C1024T、C406T进行分析鉴定。结果 137例新生儿的家系中258例患者有213例检出突变类型,45例未检出突变类型。单个位点突变184例,G1376T,66例(30.9%);G1388A,64例(30%);A95G,25例(11.7%);C1024T,16例(7.5%);G392T,10例(4.7%);C406T,3例(1.4%)。复合位点突变共29例,G871A+C1311T+IVS11 93T→C,10例(4.7%);G1376T+IVS11 93T→C,7例(3.3%);C1311T+IVS11 93T→C,5例(2.3%);C406T+C1311T,2例(0.9%);G1388A+IVS11 93T→C,2例(0.9%);G1376T+C1311T+IVS11 93T→C,1例(0.5%);A95G+C1311T+IVS11 93T→C,1例(0.5%);C1024T+IVS11 93T→C,1例(0.5%)。结论随着外来人口的流入和通婚的增多,上海地区的G6PD基因突变也在发生变化,基因诊断是对该病分子水平的诊断,有利于杂合子的检测,以便做好产前筛查,同时对研究人口迁徙与遗传病分布之间的关系有一定意义。

Objective To evaluate the mutations in newborns with glucose 6 phosphate dehydrogenase（G6PD）deficiency discovered by newborn screening,and investigate the G6PD genotypic mutation characteristics in Shanghai area as well as explore the mechanism of this disease and improve the diagnosis.Methods High resolution melting curve analysis（HRM）was used to determine G6PD mutations G1388A,G1376T,A95G,G392T,G871A,C1311T,C1024T and C406T which are common in Chinese patients.Results 213 among 258 cases from 137 families were identified to have G6PD mutations,and the remaining 45 cases were not found to harbor G6PD mutations.Among all the detected mutations,point mutations were found in 184 cases,including 66 cases（30.9%）of G1376T,64 cases（30%）of G1388A,25 cases（11.7%）of A95G,16 cases（7.5%）of C1024T,10 cases（4.7%）of G392T and 3 cases（1.4%）of C406T.Multi-point mutations were found in 29 cases,which included 10 cases（4.7%）with G871A ＋ C1311T ＋ IVS11 93T→C,7 cases（3.3%）with G1376T ＋ IVS11 93T→C,5 cases（2.3%）with C1311T ＋ IVS11 93T→C,2 cases（0.9%）with C406T ＋ C1311T,2 cases（0.9%）with G1388A ＋ IVS11 93T→C,1 case（0.5%）with G1376T ＋ C1311T ＋ IVS11 93T→C,1 case（0.5%）with A95G ＋ C1311T ＋ IVS11 93T→C and 1 case（0.5%）with C1024T ＋ IVS11 93T→C.Conclusions With the increase of the migration and intermarriage,there were changes in the characteristics of G6PD gene mutations in Shanghai.The usage of molecular diagnosis can favor the detection of heterozygotes which is useful for premarital and prenatal diagnosis for G6PD deficiency.In the meanwhile,it is of significance to understand the relationship between population migration and the distribution of genetic diseases.HRM is a new approach for genotyping analysis,with the advantages of accuracy,rapidity and high-throughput.The detection of G6PD mutations by this technique can be a supplement to regular newborn screening.