115462例新生儿葡萄糖-6-磷酸脱氢酶缺乏症筛查及基因突变分析

Screening and Genotype Survey of 115462 Neonates with Glucose-6-phosphate Dehydrogenase Deficiency

目的了解贵阳地区葡萄糖-6-磷酸脱氢酶(glucose-6-phosphate dehydrogenase,G6PD)缺乏症发病情况和基因突变特点,为贵阳地区G6PD缺乏症的防治提供科学参考。方法募集该地区2020年8月至2023年1月出生的新生儿,应用荧光分析法对其血斑样本进行G6PD酶活性筛查,召回初筛阳性儿,完成G6PD酶活性诊断及多色探针荧光PCR熔解曲线法(Multicolor probe melting curve analysis method,MMCA)基因突变分析。结果共募集115462例新生儿,G6PD酶活性筛查血斑样本共筛出阳性1606例,筛查阳性率为1.39%(1606/115462),其中男性为1.83%(1130/61801)、女性0.89%(476/53661),男女新生儿G6PD酶活性初筛阳性率差异有统计学意义(P<0.01);召回初筛阳性患儿,G6PD基因突变检出率87.07%(909/1044),其中男性为90.09%(764/848),女性为73.98%(145/196),男女间G6PD基因突变检出率差异有统计学意义(P<0.01)。本研究共检出13种类型G6PD基因单一突变型(c.1024 G>T、c.1388 G>A、c.95 A>G、c.1376 G>T、c.592C>T、c.871 G>A、c.519 C>T、c.392G>T、c.493 A>G、c.1004C>A、c.1360C>T、c.383T>C、c.517T>C)和6种复合突变型(c.1376 G>T杂合复合c.95A>G杂合突变、c.1024 G>T杂合复合c.95A>G杂合突变、c.1024 C>T杂合复合c.1388 G>A杂合突变、c.1024 C>T杂合复合c.519C>T杂合突变、c.1376 G>T杂合复合c.1024 C>T杂合突变、c.95A>G杂合复合c.1388 G>A杂合突变)。贵阳地区G6PD缺乏症基因突变类型复杂多样,G6PD突变常见类型为c.1024 C>T、c.1388G>A、c.95 A>G、c.1376G>T这四种类型。结论贵阳地区G6PD基因突变位点具有明显地域性特征,开展G6PD酶活性筛查及相关诊断检测,有利于本地区G6PD缺乏症的筛查、确诊、治疗和防控,有效提高出生人口素质。

Objective To investigate and analyze the incidence and gene mutation characteristics of glucose-6-phosphate dehydrogenase(G6PD)deficiency in Guiyang area,and to provide reference for prevention and treatment of G6PD deficiency in this region.Methods A total of 115462 neonates born in this area from August 2020 to January 2023 were screened for G6PD enzyme activity by fluorescence analysis.The positive samples were recalled and G6PD enzyme activity was diagnosed and gene mutation was analyzed by Multicolor probe melting curve analysis method(MMCA)Results It indicated that there were1606 cases were positive subjects by G6PD enzyme activity screen,and the prevalence of G6PD deficiency was 1.39%(1606/115462).The incidence of G6PD deficiency in male1.83%(1130/61801)was higher than in female 0.89%(476/53661)(P<0.01).Among MMCA genotyping analysis,the mutation rate of G6PD was 87.07%(909/1044).The mutation rate of male90.09%(824/848)was higher than female 73.98%(145/196)(P<0.01).A total of 13 kinds of single mutations(c.1024 G>T、c.1388 G>A、c.95 A>G、c.1376 G>T、c.592C>T、c.871 G>A、c.519 C>T、c.392G>T、c.493 A>G、c.1004C>A、c.1360C>T、c.383T>C、c.517T>C)and 6 kinds of compound mutations were detected.The mutations of c.1376 G>T compound c.95A>G、c.1024 G>Tcompoundc.95A>G、c.1024 C>T compound c.1388 G>A、c.1024 C>T compound c.519C>T、c.1376 G>T compound c.1024 C>T、c.95A>G compound c.1388 G>A.The types of gene mutations were complex and diverse,with c.1024 C>T、c.1388G>A、c.95 A>G、c.1376G>T being the most common mutations.Conclusions The gene mutation sites show obvious regional characteristics in Guiyang.The screening of G6PD enzyme activity and related diagnostic tests are conducive to the screening、diagnosis、treatment、prevention and control of G6PD deficiency in this region,and effectively improve the quality of the born population.