新生儿葡萄糖-6-磷酸脱氢酶缺乏症筛查及基因突变特征分析  

Screening and genetic mutation analysis of glucose-6-phosphate dehydrogenase deficiency in neonates

作　　者：张禾璇 杨雪[1] 王侣金 李林洁[1] 刘兴宇 Zhang Hexuan;Yang Xue;Wang Lyujin;Li Linjie;Liu Xingyu(Department of Eugenics and Genetics,Guiyang Maternity and Child Health Care Hospital,Guiyang 550001,Guizhou Province,China)

机构地区：[1]贵阳市妇幼保健院优生遗传科,贵阳550001

出　　处：《中华妇幼临床医学杂志（电子版）》2024年第2期200-208,共9页Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)

基　　金：贵州省科技厅临床专项科技计划项目(黔科合成果-LC〔2022〕005);贵阳市卫生健康局高层次创新型青年卫生人才培养计划项目(〔2022〕筑卫健科技合同字第001号);贵阳市科技计划项目(筑科合同〔2023〕48-25号、筑科合同GCC〔2023〕028号)。

摘　　要：目的探讨贵阳地区新生儿葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症发病情况和基因突变特点。方法选择2020年9月1日至2022年6月30日在贵阳市所有助产机构出生,并进行G6PD筛查的89715例活产新生儿为研究对象。采集其足跟血滤纸干血斑标本(DBS),采用荧光分析法定量初筛G6PD活性。对于G6PD≤27 U/dL的G6PD缺乏症初筛呈阳性新生儿,召回至贵阳市新生儿疾病筛查中心,采集空腹肘静脉血1~2 mL,采用G6PD/6-磷酸葡萄糖脱氢酶(6PGD)比值法与多色探针荧光熔解曲线(MMCA)法基因突变检测,进行新生儿G6PD缺乏症诊断。本研究经贵阳市妇幼保健院伦理委员会批准(科研伦理审查批件2021-56号),并与新生儿监护人签订临床研究知情同意书。结果本研究89715例新生儿中,G6PD缺乏症初筛阳性率为1.40%(1254/89715),其中男性新生儿的初筛阳性率为1.85%(888/47983),女性为0.88%(366/41732),男性新生儿G6PD缺乏症初筛阳性率显著高于女性,并且差异有统计学意义(χ^(2)=153.52,P<0.001)。这1254例G6PD缺乏症初筛阳性新生儿的召回复查率为74.96%(940/1254)。940例被召回复查新生儿中,被确诊为G6PD缺乏症者为895例,召回确诊率为95.21%(895/940),其中男性确诊率为98.10%(673/686),女性为87.40%(222/254);经G6PD/6PGD比值法被确诊为G6PD缺乏症者为694例,召回确诊率为73.83%(694/940),其中男性确诊率为82.51%(566/686),显著高于女性的50.39%(128/254),并且差异有统计学意义(χ^(2)=98.94,P<0.001);经MMCA法基因突变检测被确诊为G6PD缺乏症者为846例,召回确诊率为90.00%(846/940),其中男性确诊率为95.48%(655/686),显著高于女性的75.20%(191/254),差异有统计学意义(χ^(2)=84.74,P<0.001)。846例经基因突变检测确诊为G6PD缺乏症新生儿中,G6PD基因单一突变型为13种和复合杂合突变为6种,排名前4位G6PD基因热点突变类型依次为c.1024C>T(235例,占27.78%),c.1388G>A(205例,占24.23%),c.95A>G(163例,占19.27%),c.1376G>T(Objective To explore the incidence and genetic mutation characteristics of glucose-6-phosphate dehydrogenase(G6PD)deficiency in neonates of Guiyang area.Methods A total of 89715 neonates born in all delivery institutions in Guiyang from September 1,2020 to June 30,2022 and screened for G6PD deficiency were selected as research subjects.Dried blood spot of heel blood(DBS)were collected from all neonates,and fluorescence analysis method was used for the initial quantitative screening of G6PD activity.Neonates who were positive for initial screening of G6PD deficiency with G6PD≤27 U/dL were recalled to the Guiyang Neonatal Disease Screening Center.And 1-2 mL of fasting peripheral venous blood was collected from each of them,and G6PD/6-phosphogluconate dehydrogenase(6PGD)ratio method and multicolor melting curve analysis(MMCA)gene mutation detection were conducted to diagnose G6PD deficiency in neonates.This study was approved by the Ethics Committee of Guiyang Maternity and Child Health Care Hospital(Approval No.2021-56)and clinical research informed consents were obtained from the guardians of neonates.Results Among the 89715 neonates,the positive of initial screening rate for G6PD deficiency was 1.40%(1254/89715),with males at 1.85%(888/47983)and females at 0.88%(366/41732).The positive rate of initial screening for G6PD deficiency of male was statistically higher than that of female,and the difference was statistically significant(χ^(2)=153.52,P<0.001).Among the 1254 newborns who were positive for initial screening of G6PD deficiency,the recall rate was 74.96%(940/1254).Of those 940 recalled neonates,895 cases were diagnosed as G6PD deficiency,with a recall diagnosis rate of 95.21%(895/940),and the recall diagnosis rate of male was 98.10%(673/686),and the rate of female was 87.40%(222/254).For 940 recalled neonates,694 cases were diagnosed as G6PD deficiency by G6PD/6PGD ratio method,and the diagnosis rate of G6PD/6PGD ratio method was 73.83%(694/940).The diagnosis rate of male neonates by G6PD/6PGD ratio meth

关 键 词：葡糖磷酸脱氢酶 葡糖磷酸脱氢酶缺乏 新生儿筛查 G6PD基因型 基因突变 多色探针熔解曲线分析法 婴儿 新生 

分 类 号：R722.1[医药卫生—儿科]