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。

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χ²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。

①本研究胎儿Hb H病检出率为9.95%(440/4 421)。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^CSα/--^SEA(30.23%，133/440)，-α^4.2/--^SEA(14.09%，62/440)与α^WSα/--^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/β^N，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。

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高。对生育人群广泛开展地产前中海贫血筛查及其基因检测，对预防Hb H病新生儿出生缺陷具有重要意义。

To explore the prenatal diagnosis, gene mutation types and pregnancy outcome of fetal hemoglobin (Hb) H disease in Guangxi Zhuang Autonomous Region.

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 of α-Thalassemia genes (--^SEA, -α^3.7, -α^4.2) were detected by gap-crossing PCR (Gap-PCR), and the common α- and β-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.

①In this study, the overall detection rate of fetal Hb H disease was 9.95% (440/4 421). 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^CSα/--^SEA, -α^4.2/--^SEA and α^WSα/--^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 with β-Thalassemia gene mutations, and 20 cases were detected with β^CD41-42/β^N genotype, 6 cases with β^CD17/β^N, 2 cases with β^CD17/β^CD17 genotype, 2 cases with β^CD71-72/β^N, 1 case with β^CD43/β^N, and 1 case with β^-28/β^N.③Among 440 pregnant women with fetal Hb H disease, 1 case (0.23%) had spontaneous abortion, 228 cases (51.82%) chose artificial termination of pregnancy; 135 cases (30.68%) had spontaneous delivery, 65 cases (14.77%) gave birth by cesarean section; and 11 cases (2.50%) had an unknown pregnancy outcome.

The detection rate of fetal Hb H disease in Guangxi Zhuang Autonomous Region is 9.95% (440/4 421). There are various types of gene mutations, and some of them are combined with β-Thalassemia gene mutations. The proportion of pregnant women with fetal Hb H disease choosing artificial termination of pregnancy is high. Extensive implementation of Thalassemia screening and prenatal genetic diagnosis for the fertile population is of great significance for prevention and control of birth defects in Hb H disease.