摘要
目的探讨广西地区胎儿血红蛋白(Hb)H病产前诊断情况、基因突变类型及其妊娠结局。方法选择2015年1月1日至2019年12月31日,在本院接受胎儿产前地中海贫血基因检测的广西地区单胎妊娠α地中海贫血高风险胎儿中,被诊断为Hb H病的440例胎儿为研究对象。采用DNA提取试剂盒提取胎儿及其父母基因组DNA。采用跨越缺口PCR(Gap-PCR)法,检测其3种常见缺失型α地中海贫血基因(--^(SEA)、-α^(3.7)、-α^(4.2))缺失突变情况;采用PCR-反向斑点杂交法,检测其常见α、β地中海贫血基因点突变情况。对于上述常规方法检测结果未见异常,而地中海贫血筛查提示高风险的夫妇,则进一步采用多重连接探针扩增技术(MLPA)及DNA测序技术进一步进行α、β地中海贫血基因检测。对本组胎儿2015-2019年每年的胎儿Hb H病检出率比较,采用线性趋势χ^(2)检验。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求。结果①本研究胎儿Hb H病检出率为9.95%(440/4421)。2015-2019年,每年的胎儿Hb H病检出率总体比较,差异无统计学意义(P>0.05)。②在440例Hb H病胎儿中,占比前4位的Hb H病基因型分别为-α^(3.7)/--^(SEA)(39.32%,173/440),α^(CS)α/--^(SEA)(30.23%,133/440),-α^(4.2)/--^(SEA)(14.09%,62/440)与α^(WS)α/--^(SEA)(10.91%,48/440)。另外,32例Hb H病胎儿被检出同时合并β地中海贫血基因突变,其中20例被检出合并β^(CD41-42)/β^(N),6例合并β^(CD17)/βN,2例合并β^(CD17)/β^(CD17),2例合并β^(CD71-72)/β^(N)基因型,1例合并β^(CD43)/β^(N),1例合并β^(-28)/β^(N)。③妊娠440例Hb H病胎儿的孕妇中,1例(0.23%)自然流产,228例(51.82%)选择人工终止妊娠;135例(30.68%)顺产分娩,65例(14.77%)剖宫产术分娩;11例(2.50%)妊娠结局不详。结论近年广西地区胎儿Hb H的基因突变类型多样,少数合并β地中海贫血基因突变。妊娠Hb H病胎儿孕妇中,选择人工终止妊娠者的比例较�
Objective To explore the prenatal diagnosis,gene mutation types and pregnancy outcome of fetal hemoglobin(Hb)H disease in Guangxi Zhuang Autonomous Region.Methods A total of 440 fetuses diagnosed with Hb H disease were selected as research subjects in the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region from January 1,2015 to December 31,2019.The genomic DNA of fetuses and their parents was extracted by DNA extraction kit.Three common deletion mutations ofα-Thalassemia genes(--^(SEA),-α^(3.7),-α^(4.2))were detected by gap-crossing PCR(Gap-PCR),and the commonα-andβ-Thalassemia genes point mutations were detected by PCR-reverse dots blot hybridization.For couples whose test results of the above-mentioned conventional methods were normal while Thalassemia screening suggesting a high risk,multiplex ligation-dependent probe amplification(MLPA)or DNA sequencing technology was used for further testing.The detection rate of fetal Hb H disease from 2015 to 2019 was compared using linear-by-linear association chi-square test.The procedure followed in this study complied with the requirements of the World Medical Association Declaration of Helsinki revised in 2013.Results①In this study,the overall detection rate of fetal Hb H disease was 9.95%(440/4421).There was no statistically significant difference in the detection rates of fetal Hb H disease from 2015 to 2019(P>0.05).②Among 440 Hb H disease fetuses,the top 4 Hb H disease genotypes were-α^(3.7)/--^(SEA),α^(CS)α/--^(SEA),-α^(4.2)/--^(SEA) andα^(WS)α/--^(SEA),which accounting for 39.32%(173/440),30.23%(133/440),14.09%(62/440)and 10.91%(48/440),respectively.In addition,32 cases of Hb H disease fetuses were detected withβ-Thalassemia gene mutations,and 20 cases were detected withβ^(CD41-42)/β^(N) genotype,6 cases withβ^(CD17)/β^(N),2 cases withβ^(CD17)/β^(CD17) genotype,2 cases withβ^(CD71-72)/β^(N),1 case withβ^(CD43)/β^(N),and 1 case withβ^(-28)/β^(N).③Among 440 pregnant women with fetal Hb H disease,1 case(0.23%)ha
作者
王立芳
潘平山
蒙达华
林丽
左杨谨
丘小霞
Wang Lifang;Pan Pingshan;Meng Dahua;Lin Li;Zuo Yangjin;Qiu Xiaoxia(Department of Eugenics&Genetic Clinic,Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region,Nanning 530003,Guangxi Zhuang Autonomous Region,China)
出处
《中华妇幼临床医学杂志（电子版）》
CAS
2021年第1期75-80,共6页
Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)
基金
广西壮族自治区科技厅科技基地和人才专项项目(AD17129016)。
关键词
血红蛋白H
地中海贫血
基因型
基因缺失
点突变
广西壮族自治区胎儿
Hemoglobin H
alpha-Thalassemia
Genotype
Gene deletion
Point mutation
Guangxi Zhuang Autonomous Region
Fetus
