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)

[1]	Paridar M, Azizi E, Keikhaei B, et al. Iranian patients with hemoglobin H disease: genotype-phenotype correlation[J]. Mol Biol Rep, 2019，46(5)：5041-5048. DOI: 10.1007/s11033-019-04955-9.
[2]	Chen GL, Jiang F, Li J, et al. Results of coexistence of β-Thalassemia minor in Hb H disease patients[J]. Hemoglobin，2018，42(5-6)：306-309. DOI: 10.1080/03630269.2018.1561461.
[3]	Youssry I, El Badawy A, Samy RM, et al. Prevalence of α-Thalassemia in the Egyptian population[J]. Hemoglobin，2018，42(4)：243-246. DOI: 10.1080/03630269.2018.1527231.
[4]	Zhong L, Gan X, Xu L, et al. The phenomena of balanced effect between α-globin gene and of β-globin gene[J]. BMC Med Genet, 2018，19(1)：145. DOI: 10.1186/s12881-018-0659-9.
[5]	Taher AT, Vichinsky E, Musallam K, et al. Guidelines for the management of non transfusion dependent Thalassaemia(NTDT)[M]. Nicosia (Cyprus): Thalassaemia International Federation, 2013：1-24，35-46，79-83，98-101.
[6]	Liao C, Li J, Li DZ. Fetal anemia and hydrops associated with homozygosity for hemoglobin Quong Sze[J]. Prenat Diagn, 2008, 28(9): 862-864. DOI: 10.1002/pd.2058.
[7]	Komvilaisak P, Komvilaisak R, Jetsrisuparb A, et al. Fetal anemia causing hydrops fetalis from an alpha-globin variant: homozygous hemoglobin constant spring[J]. J Pediatr Hematol Oncol, 2018，40(5): 405-408. DOI: 10.1097/MPH.0000000000001051.
[8]	付春云，陈少科，张强，等. 广西地区1 571例Hb H病患者基因分型特征[J]. 中华血液学杂志，2014, 35(8): 728-731. DOI: 10.3760/cma.j.issn.0253-2727.2014.08.013.
[9]	Traivaree C, Boonyawat B, Monsereenusorn C, et al. Clinical and molecular genetic features of Hb H and AE Bart′s diseases in central Thai children[J]. Appl Clin Genet, 2018, 11: 23-30.DOI: 10.2147/TACG.S161152.
[10]	Nittayaboon K, Nopparatana C. Molecular characterization of Hb H disease in southern Thailand[J]. Int J Hematol, 2018，108(4)：384-389.DOI: 10.1007/s12185-018-2494-3.
[11]	Holtkamp N, Pistioli A, Rasenack T, et al. Identification of a novel nonsense mutation in a patient with transfusion-dependent Hb H disease[J]. Clin Lab, 2018，64(3)：371-374. DOI: 10.7754/Clin.Lab.2017.171006.
[12]	徐湘民. 地中海贫血预防控制操作指南[M]. 北京：人民军医出版社，2011：16-55，149-151.
[13]	赵芳，何小洪，程静，等. 广州地区1 571例胎儿地中海贫血产前基因型与血液学特征分析[J]. 实用医学杂志，2016, 32(21)：3562-3565.DOI: 10.3969/j.issn.1006-5725.2016.21.028.
[14]	朱晓洁，刘宇鹏，刘瑞玉，等. 惠州市同型地中海贫血夫妇的胎儿产前地中海贫血基因诊断分析[J]. 中国妇幼保健，2015, 30(19)：3270-3273.DOI: 10.7620/zgfybj.j.issn.1001-4411.2015.19.56.
[15]	林娜，黄海龙，王燕，等. 福建地区269对同型地中海贫血基因携带者夫妇产前基因诊断结果分析[J]. 中国计划生育学杂志，2016, 24(6)：395-398. DOI: 10.3969/j.issn.1004-8189.2016.06.
[16]	郭婧. 439例血红蛋白H病胎儿的临床研究[D]. 南宁：广西医科大学，2019.
[17]	Vichinsky E. Advances in the treatment of alpha-Thalassemia[J]. Blood Rev, 2012, 26(Suppl 1): S31-S34. DOI: 10.1016/S0268-960X(12)70010-3.
[18]	Zhao P, Wu H, Zhong Z, et al. Molecular prenatal diagnosis of alpha and beta Thalassemia in pregnant Hakka women in Southern China[J]. J Clin Lab Anal, 2018, 32(3)：e22306. DOI: 10.1002/jcla.22306.
[19]	Boonyawat B, Photia A, Monsereenusorn C, et al. Molecular characterization of Hb H and AE Bart′s diseases in Thai children: Phramongkutklao Hospital experiences[J]. J Med Assoc Thai, 2017, 100(2): 167-174.
[20]	Farashi S, Bayat N, Vakili S, et al. Point mutations which should not be overlooked in Hb H disease[J]. Expert Rev Hematol, 2016，9(1)：107-113. DOI: 10.1586/17474086.2016.1107470.
[21]	周玉球，肖奇志，黄丽娟，等. Hb H病患儿临床表现与基因型相关性的研究[J]. 中华儿科杂志，2004, 42(9)：693-696. DOI: 10.3760/j.issn:0578-1310.2004.09.014.
[22]	边旭明. 实用产前诊断学[M]. 北京：人民军医出版社，2008：419.
[23]	庞艳敏，王小超，潘红飞，等. 广西地区1 110例血红蛋白H病患者的基因型、血液学表型和铁过载的临床研究[J]. 右江医学，2019, 47(5): 336-342.DOI：10.3969/j.issn.1003-1383.2019.05.004.

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