石家庄地区新生儿G6PD缺乏症筛查结果及基因突变分析

Screening of Neonatal G6PD Deficiency and Gene Mutation Analysis in Shijiazhuang City

目的:明确葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症在石家庄地区新生儿中的患病率,进一步分析致病基因突变情况。方法:收集石家庄地区2018年9月—2020年11月出生的共237312例新生儿足跟血,制成滤纸干血斑,采用荧光法进行G6PD活性筛查,疑似患儿进行基因测序。结果:237312例新生儿中,筛查阳性142例,确诊114例,患病率为0.05%。114例患儿中男性105例,占92.1%,筛查结果均值(范围)为1.8(0.4~3.7)U/g Hb;女性9例,占7.9%,筛查结果均值(范围)为2.9(1.8~4.0)U/g Hb。114例患儿中56例进行了基因诊断(另外58例患儿家属拒绝进行基因诊断),56例患儿基因检测结果均为杂合突变,突变位点分析发现19种突变类型,其中16种已报道,分别为c.1376G>T、c.1024C>T、c.1388G>A、c.871G>A、c.95 A>G、c.487 G>A、c.1478 G>A、c.406 C>T、c.577 G>A、c.925A>T、c.185 A>G、c.961 G>A、c.482 G>T、c.653 C>T、c.392 G>T、c.1466 G>T;3种未见报道,分别为c.1316 G>A、c.575G>C、c.1400 C>T;突变频率较高的分别为c.1376G>T(0.25)、c.1024C>T(0.16)、c.1388G>A(0.14)。结论:初步明确了G6PD缺乏症在石家庄地区新生儿中的患病率;进一步明确了基因突变位点的分布情况;发现了3种新的基因突变类型,丰富了基因突变的数据库。

Objective:To carry out the screening of glucose-6-phosphate dehydrogenase(G6PD)deficiency in newborns in Shijiazhuang City,and to further analyze the mutations of disease genes.Methods:The heel blood of 237312 newborns born in Shijiazhuang City,from September 2018 to November 2020,was collected and made the dried blood spots on filter paper.G6PD activity was screened by fluorescence method,and the suspected children were analyzed further by gene sequencing.Results:Among 237312 newborns,142 cases were positive and 114 cases were confirmed.The prevalence rate was 0.05%.Among the 114 children,105 were males,accounting for 92.1%.The average screening result(range)was 1.8(0.4~3.7)U/g Hb;9 cases were female,accounting for 7.9%,the average screening result(range)was 2.9(1.8~4.0)U/g Hb.56 of 114 children underwent genetic diagnosis(the family members of the other 58 children refused to perform genetic diagnosis).The genetic test showed that all of 56 children had heterozygous mutations.The analysis of mutation sites revealed 19 types of mutations,of which 16 have been reported,c.1376G>T,c.1024C>T,c.1388G>A,c.871G>A,c.95 A>G,c.487 G>A,c.1478 G>A,c.406 C>T,c.577 G>A,c.925A>T,c.185 A>G,c.961 G>A,c.482 G>T,c.653 C>T,c.392 G>T,c.1466 G>T;3 kinds have not been reported,respectively c.1316 G>A,c.575G>C,c.1400 C>T.The higher mutation frequencies were c.1376G>T(0.25),c.1024C>T(0.16)and c.1388G>A(0.14).Conclusions:The prevalence of G6PD deficiency was preliminarily clarified as 0.05%in newborns in Shijiazhuang area.The distribution of gene mutation sites was further clarified.Three unreported gene mutations were discovered,which enriched the database of gene mutations of G6PD deficiency.