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Molecular characteristics of thalassemia and hemoglobin variants in prenatal diagnosis program in northern Thailand

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Abstract

Molecular analysis of globin genes is an essential process for prenatal diagnosis (PND) of severe thalassemia. This study aimed to describe the molecular characteristics of thalassemia and hemoglobin (Hb) variants in PND program in northern Thailand. The type and frequency of globin gene mutations from 1290 couples at risk of fetal severe thalassemia diseases that were tested at Thalassemia Laboratory at Chiang Mai University from 2012 to 2017 were retrospectively reviewed. The PND program detected 444 (34.4%), 196 (15.2%) and 642 (49.8%) couples at risk of fetal Hb Bart’s hydrops fetalis, beta-thalassemia major (BTM) and beta-thalassemia/Hb E disease, respectively. Coinheritance of more than one type of thalassemia was common and eight (0.6%) couples were at risk of two types of severe thalassemia. There were two types of alpha0-thalassemia; 893 (99.7%) Southeast Asian and 3 (0.3%) Thai deletions. Twenty beta-globin gene mutations were found with 94.3% of beta0-thalassemia. The codon 41/42 (− TTCT), codon 17 (A>T), IVS-I-1 (G>T) and codon 71/72 (+ A) comprised 90% of beta-thalassemia mutations. The study shows a high percentage of couples at risk of fetal Hb Bart’s hydrops fetalis and BTM. The percentage of beta0-thalassemia is higher than those seen in other regions of Thailand.

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References

  1. Higgs DR, Thein SL, Wood WG. Thalassaemia: classification, genetics and relationship to other inherited disorders of haemoglobin. In: Weatherall DJ, Clegg JB, editors. The thalassaemia syndromes. Oxford: Blackwell Science; 2001. p. 121–32.

    Google Scholar 

  2. Fucharoen S, Weatherall DJ. Progress toward the control and management of the thalassemias. Hematol Oncol Clin North Am. 2016;30:359–71.

    Article  PubMed  Google Scholar 

  3. Fucharoen S, Winichagoon P. Prevention and control of thalassemia in Asia. Asian Biomed. 2007;1:1–6.

    Google Scholar 

  4. Tongsong T, Charoenkwan P, Sirivatanapa P, Wanapirak C, Piyamongkol W, Sirichotiyakul S, et al. Effectiveness of the model for prenatal control of severe thalassemia. Prenat Diagn. 2013;33:477–83.

    Article  PubMed  Google Scholar 

  5. Wanapirak C, Muninthorn W, Sanguansermsri T, Dhananjayanonda P, Tongsong T. Prevalence of thalassemia in pregnant women at Maharaj Nakorn Chiang Mai hospital. J Med Assoc Thai. 2004;87:1415–8.

    PubMed  Google Scholar 

  6. Wong P, Thanormrat P, Srithipayawan S, Jermnim N, Niyomthom S, Nimnuch N, et al. Risk of a couple having a child with severe thalassemia syndrome, prevalence in lower northern Thailand. Southeast Asian J Trop Med Public Health. 2006;37:366–9.

    PubMed  Google Scholar 

  7. Nuinoon M, Kruachan K, Sengking W, Horpet D, Sungyuan U. Thalassemia and hemoglobin e in southern Thai blood donors. Adv Hematol. 2014;2014:932306.

    PubMed  PubMed Central  Google Scholar 

  8. Tritipsombut J, Sanchaisuriya K, Phollarp P, Bouakhasith D, Sanchaisuriya P, Fucharoen G, et al. Micromapping of thalassemia and hemoglobinopathies in different regions of northeast Thailand and Vientiane, Laos People’s Democratic Republic. Hemoglobin. 2012;36:47–56.

    Article  CAS  PubMed  Google Scholar 

  9. Charoenkwan P, Teerachaimahit P, Sanguansermsri T. The correlation of alpha-globin gene mutations and the XmnI polymorphism with clinical severity of Hb E/beta-thalassemia. Hemoglobin. 2014;38:335–8.

    Article  CAS  PubMed  Google Scholar 

  10. Sirichotiyakul S, Saetung R, Sanguansermsri T. Analysis of beta-thalassemia mutations in northern Thailand using an automated fluorescence DNA sequencing technique. Hemoglobin. 2003;27:89–95.

    Article  CAS  PubMed  Google Scholar 

  11. Viprakasit V, Limwongse C, Sukpanichnant S, Ruangvutilert P, Kanjanakorn C, Glomglao W, et al. Problems in determining thalassemia carrier status in a program for prevention and control of severe thalassemia syndromes: a lesson from Thailand. Clinical Chem Lab Med. 2013;51:1605–14.

    CAS  Google Scholar 

  12. Yamsri S, Sanchaisuriya K, Fucharoen G, Sae-Ung N, Fucharoen S. Genotype and phenotype characterizations in a large cohort of beta-thalassemia heterozygote with different forms of alpha-thalassemia in northeast Thailand. Blood Cells Mol Dis. 2011;47:120–4.

    Article  PubMed  Google Scholar 

  13. Charoenkwan P, Sirichotiyakul S, Phusua A, Suanta S, Fanhchaksai K, Sae-Tung R, et al. High-resolution melting analysis for prenatal diagnosis of beta-thalassemia in northern Thailand. Int J Hematol. 2017;106:757–64.

    Article  PubMed  Google Scholar 

  14. Pharephan S, Sirivatanapa P, Makonkawkeyoon S, Tuntiwechapikul W, Makonkawkeyoon L. Prevalence of alpha-thalassaemia genotypes in pregnant women in northern Thailand. Indian J Med Res. 2016;143:315–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pongjantharasatien K, Banyatsuppasin W, Pounsawat S, Jindadamrongwech S. Occurrence of the—-(SEA),—-(THAI) and—-(FIL) alpha-thalassemia-1 carriers from a 7-year study at Ramathibodi Hospital, Bangkok, Thailand. Hemoglobin. 2016;40:283–4.

    Article  CAS  PubMed  Google Scholar 

  16. Traivaree C, Boonyawat B, Monsereenusorn C, Rujkijyanont P, Photia A. Clinical and molecular genetic features of Hb H and AE Bart’s diseases in central Thai children. Appl Clin Genet. 2018;11:23–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Charoenkwan P, Taweephon R, Sae-Tung R, Thanarattanakorn P, Sanguansermsri T. Molecular and clinical features of Hb H disease in northern Thailand. Hemoglobin. 2005;29:133–40.

    Article  CAS  PubMed  Google Scholar 

  18. Nittayaboon K, Nopparatana C. Molecular characterization of Hb H disease in southern Thailand. Int J Hematol. 2018;108:384–9.

    Article  CAS  PubMed  Google Scholar 

  19. Li DZ, Li Y, Li J, Li SC, Li R. Prevention of Hb Bart’s (gamma4) disease associated with the—-(THAI) alpha(0)-thalassemia deletion in Mainland China. Hemoglobin. 2015;39:412–4.

    Article  CAS  PubMed  Google Scholar 

  20. Lai K, Li S, Lin W, Yang D, Chen W, Li M, et al. Invasive prenatal diagnosis of alpha-thalassemia to control Hb Bart’s hydrops fetalis syndrome: 15 years of experience. Arch Gynecol Obstet. 2018;298:307–11.

    Article  PubMed  Google Scholar 

  21. Peng CT, Liu SC, Peng YC, Lin TH, Wang SJ, Le CY, et al. Distribution of thalassemias and associated hemoglobinopathies identified by prenatal diagnosis in Taiwan. Blood Cells Mol Dis. 2013;51:138–41.

    Article  PubMed  Google Scholar 

  22. Boonyawat B, Monsereenusorn C, Traivaree C. Molecular analysis of beta-globin gene mutations among Thai beta-thalassemia children: results from a single center study. Appl Clin Genet. 2014;7:253–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Thein SL, Winichagoon P, Hesketh C, Best S, Fucharoen S, Wasi P, et al. The molecular basis of beta-thalassemia in Thailand: application to prenatal diagnosis. Am J Hum Genet. 1990;47:369–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Laosombat V, Fucharoen SP, Panich V, Fucharoen G, Wongchanchailert M, Sriroongrueng W, et al. Molecular basis of beta thalassemia in the south of Thailand. Am J Hematol. 1992;41:194–8.

    Article  CAS  PubMed  Google Scholar 

  25. Vo LTT, Nguyen TT, Le HX, Le HTT. Analysis of common beta-thalassemia mutations in North Vietnam. Hemoglobin. 2018;42:16–22.

    Article  CAS  PubMed  Google Scholar 

  26. Win N, Harano T, Harano K, Myint TT, Mra R, Okada S, et al. A wider molecular spectrum of beta-thalassaemia in Myanmar. Br J Haematol. 2002;117:988–92.

    Article  CAS  PubMed  Google Scholar 

  27. Wongprachum K, Sanchaisuriya K, Dethvongphanh M, Norcharoen B, Htalongsengchan B, Vidamaly V, et al. Molecular heterogeneity of thalassemia among pregnant laotian women. Acta Haematol. 2016;135:65–9.

    Article  CAS  PubMed  Google Scholar 

  28. Yatim NF, Rahim MA, Menon K, Al-Hassan FM, Ahmad R, Manocha AB, et al. Molecular characterization of alpha- and beta-thalassaemia among Malay patients. Int J Mol Sci. 2014;15:8835–45.

    Article  CAS  PubMed  Google Scholar 

  29. Yin A, Li B, Luo M, Xu L, Wu L, Zhang L, et al. The prevalence and molecular spectrum of alpha- and beta-globin gene mutations in 14,332 families of Guangdong Province, China. PloS One. 2014;9:e89855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhao P, Wu H, Weng R. Molecular analysis of hemoglobinopathies in a large ethnic Hakka population in southern China. Medicine (Baltimore). 2018;97:e13034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Komvilaisak P, Komvilaisak R, Jetsrisuparb A, Wiangnon S, Jirapradittha J, Kiatchoosakun P, et al. Fetal anemia causing hydrops fetalis from an alpha-globin variant: homozygous hemoglobin constant spring. J Pediatr Hematol Oncol. 2018;40:405–8.

    Article  PubMed  Google Scholar 

  32. He Y, Zhao Y, Lou JW, Liu YH, Li DZ. Fetal anemia and hydrops fetalis associated with homozygous Hb Constant Spring (HBA2: c.427T > C). Hemoglobin. 2016;40:97–101.

    Article  CAS  PubMed  Google Scholar 

  33. Charoenkwan P, Sirichotiyakul S, Chanprapaph P, Tongprasert F, Taweephol R, Sae-Tung R, et al. Anemia and hydrops in a fetus with homozygous hemoglobin constant spring. J Pediatr Hematol Oncol. 2006;28:827–30.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank the Thalassemia laboratory staff at the Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, for their assistance.

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, Chiang Mai University, 110 Intawarorot road, Sriphum, Muang, Chiang Mai, Thailand

    Kanittha Mankhemthong, Arunee Phusua, Sudjai Suanta, Pitipong Srisittipoj, Pimlak Charoenkwan & Torpong Sanguansermsri

  2. Thalassemia Research Unit, Institute of Human Genetics, University of Phayao, Phayao, Thailand

    Torpong Sanguansermsri

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  1. Kanittha Mankhemthong
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  2. Arunee Phusua
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  3. Sudjai Suanta
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  5. Pimlak Charoenkwan
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Correspondence to Pimlak Charoenkwan.

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Mankhemthong, K., Phusua, A., Suanta, S. et al. Molecular characteristics of thalassemia and hemoglobin variants in prenatal diagnosis program in northern Thailand. Int J Hematol 110, 474–481 (2019). https://doi.org/10.1007/s12185-019-02694-y

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  • DOI: https://doi.org/10.1007/s12185-019-02694-y

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