Skip to main content
SpringerLink
Log in

Prenatal diagnosis of α- and β-thalassemias in southern Thailand

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

We report our work on prenatal diagnosis of α-thalassemia, β-thalassemia and other hemoglobinopathies in southern Thailand. DNA-based diagnosis was offered to 1906 pregnancies at risk for thalassemia using a combination method of multiplex-PCR and reverse dot blot analysis to detect seven α-globin and 47 β-globin mutations. The most commonly detected mutation of α0-thalassemia was a South-East Asian deletion (98%), followed by a Thai deletion (2%). Twenty-eight β-globin mutations were identified. Fourteen common mutations, including cod 19 A-G (18.6%), cod 41/42 -TCTT (14.4%), IVS1#5 G-C (13.2%), 3.5 kb deletion (9.2%), cod 17 A-T (7.7%), -28 A-G (7.3%), IVSI#1 G-T (7.1%), 12.5 kb deletion (δβ)0 (5.7%), HPFH6 (4.2%), IVS2#654 C-T (2.7%), 45 kb deletion (1.9%), Asian Indian-inversion-deletion Gγ(Aγδβ)0 (1.6%), cod 41 -C (1.5%) and cod 71/72 +A (1.3%) were detected, accounting for 96.5% of all mutations detected. The most common hemoglobin variant was Hb E, accounting for 97.86%. Prenatal diagnosis of 1906 couples at risk showed 22.0% normal, 51.2% carrier and 26.8% affected. The present study provides important information for diagnosis and control of severe thalassemia diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Fucharoen S, Winichagoon P. Haemoglobinopathies in Southeast Asia. Indian J Med Res. 2011;134(4):498–506.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008;86(6):480–7.

    Article  Google Scholar 

  3. Origa R, Moi P (2016) [Internet]. Alpha-thalassemia. GeneReviews® [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK1435/. Cited 2018 May 15.

  4. Chui DHK. Thalassemia: Hb H disease and Hb Bart’s hydrops fetalis. Ann NY Acad Sci. 2005;1054:25–32.

    Article  CAS  Google Scholar 

  5. Nittayaboon K, Nopparatana C. Molecular characterization of Hb H disease in southern Thailand. Int J Hematol. 2018;108(4):384–9.

    Article  CAS  Google Scholar 

  6. Giardine B, van Baal S, Kaimakis P, Riemer C, Miller W, Samara M, et al. HbVar database of human hemoglobin variants and thalassemia mutations: 2007 update. Hum Mutat. 2007;28(2):206–16.

    Article  Google Scholar 

  7. Nopparatana C, Panich V, Saechan V, Sriroongrueng V, Nopparatana C, Rungjeadpha J, et al. The spectrum of beta-thalassemia mutations in southern Thailand. Southeast Asian J Trop Med Public Health. 1995;26(Suppl 1):229–34.

    PubMed  Google Scholar 

  8. 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(3):369–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Weatherall D. The Thalassemias: the role of molecular genetics in an evolving global health problem. Am J Hum Genet. 2004;74(3):385–92.

    Article  CAS  Google Scholar 

  10. Winichagoon P, Fucharoen S, Thonglairoam V, Tanapotiwirut V, Wasi P. β-thalassemia in Thailand. Ann N Y Acad Sci. 1990;612(1):31–42.

    Article  CAS  Google Scholar 

  11. Fucharoen S, Weatherall DJ. The hemoglobin E thalassemias. Cold Spring Harb Perspect Med. 2012;2(8):a011734. https://doi.org/10.1101/cshperspect.a011734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Thein SL. The Molecular basis of β-thalassemia. Cold Spring Harb Perspect Med. 2013;3(5):a011700. https://doi.org/10.1101/cshperspect.a011700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bhattyacharyya M, Bagchi B, Kumar M. A study of phenotypic heterogeneity in Hb E-beta thalassemia and its correlation with Hb E Level. Blood. 2014;124(21):1365.

    Article  Google Scholar 

  14. Fucharoen S, Pengjam Y, Surapot S, Fucharoen G, Sanchaisuriya K. Molecular and hematological characterization of HPFH-6/Indian deletion-inversion Ggamma(Agammadeltabeta)0-thalassemia and Ggamma(Agammadeltabeta)0-thalassemia/HbE in Thai patients. Am J Hematol. 2002;71(2):109–13.

    Article  CAS  Google Scholar 

  15. Winichagoon P, Fucharoen S, Thonglairoam V, Wasi P. Thai Ggamma (Agamma delta beta)zero-thalassemia and its interaction with a single gamma-globin gene on a chromosome carrying beta zero-thalassemia. Hemoglobin. 1990;14(2):185–97.

    Article  CAS  Google Scholar 

  16. Singha K, Fucharoen G, Hama A, Fucharoen S. A novel (A)γδβ(0)-thalassemia caused by DNA deletion-inversion-insertion of the β-globin gene cluster and five olfactory receptor genes: genetic interactions, hematological phenotypes and molecular characterization. Clin Biochem. 2015;48(10–11):703–8.

    Article  CAS  Google Scholar 

  17. Modell B (2007) Epidemiological estimates for haemoglobin disorders: WHO South East Asian Region by Country. Bull World Health Organ 2007 [cited 2018 May 15]. http://www.modell-almanac.net/world.sear.pdf.

  18. Fucharoen S, Winichagoon P. New updating into hemoglobinopathies. Int J Lab Hematol. 2012;34(6):559–65.

    Article  CAS  Google Scholar 

  19. Fucharoen S, Winichagoon P. Thalassemia in Southeast Asia: problems and strategy for prevention and control. Southeast Asian J Trop Med Public Health. 1992;23(4):647–55.

    CAS  PubMed  Google Scholar 

  20. Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ. 2001;79(8):704–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kor-Anantakul O, Suwanrath C, Leetanaporn R, Suntharasaj T, Liabsuetrakul T, Rattanaprueksachat R. Prenatal diagnosis of thalassemia in Songklanagarind Hospital in Southern Thailand. Southeast Asian J Trop Med Public Health. 1998;29(4):795–800.

    CAS  PubMed  Google Scholar 

  22. Nopparatana C, Saechan V, Nopparatana C, Pornpatkul M, Panich V, Fukumaki Y. A novel 105 basepair deletion causing beta(0)-thalassemia in members of a Thai family. Am J Hematol. 1999;61(1):1–4.

    Article  CAS  Google Scholar 

  23. Winichagoon P, Saechan V, Sripanich R, Nopparatana C, Kanokpongsakdi S, Maggio A, et al. Prenatal diagnosis of beta-thalassaemia by reverse dot-blot hybridization. Prenat Diagn. 1999;19(5):428–35.

    Article  CAS  Google Scholar 

  24. Cai SP, Wall J, Dan YW, Chehab FF. Reverse dot blot probes for the screening of β-thalassemia mutations in Asians and American Blacks. Hum Mutat. 1994;3(1):59–63.

    Article  CAS  Google Scholar 

  25. Craig JE, Barnetson RA, Prior J, Raven JL, Thein SL. Rapid detection of deletions causing delta beta thalassemia and hereditary persistence of fetal hemoglobin by enzymatic amplification. Blood. 1994;83:1673–82.

    Article  CAS  Google Scholar 

  26. Sun H, Liu H, Huang K, Lin K, Huang X, Chu J, et al. β-globin gene cluster haplotypes in ethnic minority populations of southwest China. Sci Rep. 2017;7:42909. https://doi.org/10.1038/srep42909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Budowle B, Chakraborty R, Glusti AM, Eisenberg AJ, Allen RC. Analysis of VNTR Locus D1S80 by the PCR followed by high-resolution PAGE. Am J Hum Genet. 1991;48(1):137–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Decorte R, Cuppens H, Marynen P, Cassiman JJ. Rapid detection of hypervariable regions by the polymerase chain reaction technique. DNA Cell Biol. 1990;9(6):461–9.

    Article  CAS  Google Scholar 

  29. Tongsong T, Wanapirak C, Sirivatanapa P, Sanguansermsri T, Sirichotiyakul S, Piyamongkol W, et al. Prenatal control of severe thalassaemia: Chiang Mai strategy. Prenat Diagn. 2000;20(3):229–34.

    Article  CAS  Google Scholar 

  30. Yamsri S, Sanchaisuriya K, Fucharoen G, Sae-Ung N, Ratanasiri T, Fucharoen S. Prevention of severe thalassemia in northeast Thailand: 16 years of experience at a single university center. Prenat Diagn. 2010;30:540–6.

    PubMed  Google Scholar 

  31. 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;10(7):253–8.

    Google Scholar 

  32. Yang KG, Kutlan F, George E, Wilson JB, Kutlar A, Stoming TA, et al. Molecular characterization of β globin gene mutations in Malay patients with HbE-β-thalassemia and thalassemia major. Br J Haematol. 1989;72(1):73–80.

    Article  CAS  Google Scholar 

  33. Panigrahi I, Marwaha RK. Mutational spectrum of thalassemias in India. Indian J Hum Genet. 2007;13(1):36–7.

    Article  CAS  Google Scholar 

  34. Olivieri NF, Pakbaz Z, Vichinsky E. Hb E/beta-thalassaemia: a common & clinically diverse disorder. Indian J Med Res. 2011;134(4):522–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Weatherall DJ. Hemoglobin E β-thalassemia: an increasingly common disease with some diagnostic pitfalls. J Pediatr. 1998;132(5):765–7.

    Article  CAS  Google Scholar 

  36. Fucharoen S, Winichagoon P, Thonglairoam V, Siriboon W, Siritanaratkul N, Kanokpongsakdi S, et al. Prenatal diagnosis of thalassemia and hemoglobinopathies in Thailand: experience from 100 pregnancies. Southeast Asian J Trop Med Public Health. 1991;22(1):16–29.

    CAS  PubMed  Google Scholar 

  37. Mankhemthong K, Phusua A, Suanta S, Srisittipoj P, Charoenkwan P, Sanguansermsri T. Molecular characteristics of thalassemia and hemoglobin variants in prenatal diagnosis program in northern Thailand. Int J Hematol. 2019. https://doi.org/10.1007/s12185-019-02694-y.

    Article  PubMed  Google Scholar 

  38. Yamsri S, Sanchaisuriya K, Fucharoen G, Sae-ung N, Ratanasiri T, Fucharoen S. Prevention of severe thalassemia in northeast Thailand: 16 years of experience at a single university center. Prenat Diagn. 2010;30:540–6.

    PubMed  Google Scholar 

  39. Buakhao J, Khumpun P, Winichagoon P, Fucharoen S, Paiboonsukwong K. Prevalence and characterization of thalassemia among migrant workers from Cambodia, Lao PDR and Myanmar in Thailand. Southeast Asian J Trop Med Public Health. 2017;48:864–74.

    Google Scholar 

  40. Ahmad R, Saleem M, Aloysious NS, Yelumalai P, Mohamed N, Hassan S. Distribution of alpha thalassaemia gene variants in diverse ethnic populations in Malaysia: data from the Institute for Medical Research. Int J Mol Sci. 2013;14:18599–614. https://doi.org/10.3390/ijms140918599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the staff of Hematology and Thalassemia Laboratory of the Department of Pathology for technical support. The authors would also like to thank the staff of the Antenatal Care Unit and Maternal-Fetal Medicine Unit of the Department of Obstetrics and Gynecology for genetic counseling and fetal specimen collection. This research was supported by a grant (MED36202) from Faculty of Medicine, Prince of Songkla University and National Research Council of Thailand. This study was approved by the ethics committee of the Faculty of Medicine, Prince of Songkla University (REC.61-307-5-2).

Author information

Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, 90110, Thailand

    Chamnong Nopparatana, Chawadee Nopparatana, Sataron Karnchanaopas & Korntip Srewaradachpisal

  2. Faculty of Veterinary Science, Prince of Songkla University, Songkhla, 90110, Thailand

    Vannarat Saechan

Authors
  1. Chamnong Nopparatana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chawadee Nopparatana
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vannarat Saechan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sataron Karnchanaopas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Korntip Srewaradachpisal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Chamnong designed the research study, interpreted the data, and wrote the manuscript. Chawadee, Vannarat, Sataron, and Korntip performed the research and collected the data. The final version of the article was read and approved by all of the authors.

Corresponding author

Correspondence to Chamnong Nopparatana.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests regarding the publication of this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nopparatana, C., Nopparatana, C., Saechan, V. et al. Prenatal diagnosis of α- and β-thalassemias in southern Thailand. Int J Hematol 111, 284–292 (2020). https://doi.org/10.1007/s12185-019-02761-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-019-02761-4

Keywords

Search

Navigation