Prenatal diagnosis of 440 fetuses with hemoglobin H disease in Guangxi area

doi:10.3877/cma.j.issn.1673-5250.2021.01.011

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 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.

Results

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.

Conclusions

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.

Key words: Hemoglobin H, alpha-Thalassemia, Genotype, Gene deletion, Point mutation, Guangxi Zhuang Autonomous Region, Fetus

表1 2015-2019年，本研究各年份胎儿Hb H病检出率比较[例数(%)]

时间(年)	胎儿例数	Hb H病胎儿
2015	453	52(11.48)
2016	811	90(11.01)
2017	832	88(10.58)
2018	1 254	124(9.89)
2019	1 071	86(8.03)
χ²值		7.149
P值		0.128

表1 2015-2019年，本研究各年份胎儿Hb H病检出率比较[例数(%)]

时间(年)	胎儿例数	Hb H病胎儿
2015	453	52(11.48)
2016	811	90(11.01)
2017	832	88(10.58)
2018	1 254	124(9.89)
2019	1 071	86(8.03)
χ²值		7.149
P值		0.128

表2 440例胎儿Hb H病基因型分布[例数(%)]

α地中海贫血基因型	构成比	α地中海贫血基因型	构成比
-α^3.7/--^SEA	173(39.32)	α^CSα/α^CSα	6(1.36)
α^CSα/--^SEA	133(30.23)	α^CSα/--^THAI	2(0.45)
-α^4.2/--^SEA	62(14.09)	-α^4.2/--^THAI	1(0.23)
α^WSα/--^SEA	48(10.91)	-α^3.7/--^THAI	1(0.23)
α^QSα/--^SEA	14(3.18)

表2 440例胎儿Hb H病基因型分布[例数(%)]

α地中海贫血基因型	构成比	α地中海贫血基因型	构成比
-α^3.7/--^SEA	173(39.32)	α^CSα/α^CSα	6(1.36)
α^CSα/--^SEA	133(30.23)	α^CSα/--^THAI	2(0.45)
-α^4.2/--^SEA	62(14.09)	-α^4.2/--^THAI	1(0.23)
α^WSα/--^SEA	48(10.91)	-α^3.7/--^THAI	1(0.23)
α^QSα/--^SEA	14(3.18)

表3 440例Hb H病胎儿妊娠结局分析[例数(%)]

妊娠结局	发生率
人工终止妊娠	228(51.82)
顺产	135(30.68)
剖宫产术分娩	65(14.77)
自然流产	1(0.23)
妊娠结局未知	11(2.50)
合计	440(100.00)

表3 440例Hb H病胎儿妊娠结局分析[例数(%)]

妊娠结局	发生率
人工终止妊娠	228(51.82)
顺产	135(30.68)
剖宫产术分娩	65(14.77)
自然流产	1(0.23)
妊娠结局未知	11(2.50)
合计	440(100.00)

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