Rare β-Globin Gene Mutations including a de novo Mutation of Hemoglobin Hammersmith in Southern Thailand
DOI:
https://doi.org/10.31584/jhsmr.2020741Keywords:
hemoglobinopathy, rare mutation, southern Thailand, β-globin geneAbstract
Objective: The aim of this study was to characterize unknown β-globin gene mutations in individuals who attended Songklanagarind Hospital for thalassemia screening and genetic counseling.
Material and Methods: β-thalassemia mutations in individuals with hemoglobin (Hb) A2 levels >3.5% originating from various provinces in southern Thailand were characterized by reverse dot blot hybridization (RDB) and multiplex gappolymerase chain reaction using a panel of 30 allele-specific probes for point mutations and 6 sets of specific primers for large deletions. Mutations which could not be identified by these two methods were further analyzed by direct deoxyribonucleic acid (DNA) sequencing.
Results: Nineteen subjects found to have uncharacterized β-globin gene mutations were analyzed by direct DNA sequencing. Nine different rare mutations were identified, four of which have not been to date described in Thailand: -30 (T>C), codon 5 (-CT), Hb Monroe (codon 30, G>C) and Hb Hammersmith (codon 42, T>C). An Hb Hammersmith mutation detected in one subject appeared to be a spontaneous mutation, unrelated to family history. The other five mutations have been reported previously within Thailand, but here they were identified in the southern part of Thailand for the first time: -31 (A>G), codon 15 (-T), codon 35 (C>A), codon 95 (+A) and Hb Dhonburi (codon 126, T>G). The presence of the mutations was confirmed by RDB.
Conclusion: In addition to the already reported β-globin gene mutations, 9 other different types of mutations were identified. This information should be useful for planning genetic counseling and prenatal diagnosis programs for prevention and control of thalassemia diseases.
References
1. Fucharoen S, Winichagoon P. Haemoglobinopathies in Southeast Asia. Indian J Med Res 2011;134:498-506.
2. 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.
3. Modell B. Epidemiological estimates for haemoglobin disorders: WHO South East Asian Region by Country. Bull World Health Organ [serial on the Internet]. 2007 [cited 2019 Oct 1]. Available from: http://www.modell-almanac.net/world. sear.pdf
4. Nopparatana C, Panich V, Saechan V, Sriroongrueng V, Nopparatana C, Rungjeadpha J, et al. The spectrum of betathalassemia mutations in southern Thailand. Southeast Asian J Trop Med Public Health 1995;26(Suppl 1):S229-34.
5. Sutcharitchan P, Saiki R, Fucharoen S, Winichagoon P, Erlich H, Embury SH. Reverse dot-blot detection of Thai betathalassaemia mutations. Br J Haematol 1995;90:809-16.
6. 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;71:109-13.
7. 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;48:137-44.
8. Cai SP, Zhang JZ, Doherty M, Kan YW. A new TATA box mutation detected at prenatal diagnosis for beta-thalassemia. Am J Hum Genet 1989;45:112-4.
9. Sanchaisuriya K, Fucharoen S, Fucharoen G, Ratanasiri T, Sanchaisuriya P, Changtrakul Y, et al. A reliable screening protocol for thalassemia and hemoglobinopathies in pregnancy: an alternative approach to electronic blood cell counting. Am J Clin Pathol 2005;123:113-8.
10. Kollia P, Gonzalez-Redondo JM, Stoming TA, Loukopoulos D, Politis C, Huisman TH. Frameshift codon 5 [Fsc-5 (-CT)] thalassemia; a novel mutation detected in a Greek patient. Hemoglobin 1989;13:597-604.
11. Agarwal S, Hattori Y, Agarwal SS. Rare beta-thalassemia mutations in Asian Indians. Am J Hematol 2000;65:322-3.
12. Akhavan-Niaki H, Derakhshandeh-Peykar P, Banihashemi A, Mostafazadeh A, Asghari B, Ahmadifard MR, et al. A comprehensive molecular characterization of beta-thalassemia in a highly heterogeneous population. Blood Cells Mol Dis 2011;47:29-32.
13. Zahed L. The Spectrum of beta-Thalassemia mutations in the Arab Populations. J Biomed Biotechnol 2001;1:129-32.
14. Zhang J, Zhu BS, He J, Zeng XH, Su J, Xu XH, et al. The spectrum of α- and β-thalassemia mutations in Yunnan province of Southwestern China. Hemoglobin 2012;36:464- 73.
15. Vidaud M, Gattoni R, Stevenin J, Vidaud D, Amselem S, Chibani J, et al. A 5' splice-region G----C mutation in exon 1 of the human beta-globin gene inhibits pre-mRNA splicing: a mechanism for beta+-thalassemia. Proc Natl Acad Sci U S A 1989;86:1041-5.
16. Gonzalez-Redondo JM, Stoming TA, Lanclos KD, Gu YC, Kutlar A, Kutlar F, et al. Clinical and genetic heterogeneity in black patients with homozygous beta-thalassemia from the southeastern United States. Blood 1988;72:1007-14.
17. Hamid M, Shariati G, Saberi A, Kaikhaei B, Galehdari H,Mohammadi-Anaei M. Identification of IVS-I (-1) (G > C) or Hb Monroe as a report on the beta-globin gene with a betathalassemia minor phenotype in south of Iran. Arch Iran Med 2013;16:563-4.
18. Piammongkol S, Chongsuvivatwong V, Williams G, Pornpatkul M. The prevalence and determinants of iron deficiency anemia in rural Thai-Muslim pregnant women in Pattani province. Southeast Asian J Trop Med Public Health 2006;37: 553-8.
19. Dacie JV, Shinton NK, Gaffney PJ Jr, Lehmann H. Haemoglobin Hammersmith (beta-42 (CDI) Phe replaced by ser). Nature 1967;216:663-5.
20. Akiyama M, Murayama S, Yokoi K, Yanagisawa T, Hattori Y, Yamashiro Y, et al. Hemoglobin Hammersmith [beta 42(CD1) Phe --> Ser] causing severe hemolytic anemia in a Japanese girl. Pediatr Blood Cancer 2006;47:839-41.
21. Rahbar S, Feagler RJ, Beutler E. Hemoglobin Hammersmith (beta 42 (CD1) Phe replaced by Ser) associated with severe hemolytic anemia. Hemoglobin 1981;5:97-105.
22. Cunningham TA, Baker F, Kobrinsky NL, Cepreganova B, Baysal E, Wilson JB, et al. The unstable Hb Hammersmith or alpha2 beta2(42)(CD1)Phe----Ser observed in an Indian child; identification by HPLC and by sequence analysis of amplified DNA. Hemoglobin 1992;16:19-25.
23. Rahbar S, Bennetts GA, Ettinger LJ. Hemoglobin Hammersmith as the cause of severe hemolytic anemia in a Chinese girl. Am J Pediatr Hematol Oncol 1986;8:13-7.
24. Tuohy AM , McKie VC, Sabio H, Kutlar F, Kutlar A, Wilson JB. Hb Hammersmith [beta 42(CD1) Phe-->Ser]: occurrence as a de novo mutation in black monozygotic twins with multiple congenital anomalies. J Pediatr Hematol Oncol 1998;20:563-6.
25. Sonati MF, Kimura EM, Abreu CF, Oliveira DM, Pinheiro VR, Costa FF. Hemoglobin Hammersmith [beta 42 (CD1) Phe --> Ser] in a Brazilian girl with congenital Heinz body hemolytic anemia. Pediatr Blood Cancer 2006;47:855-6.
26. Park S, Kang HJ, Cho SI, Kim SY, Seong MW, Park SS. A case report of a male patient with Hb Hammersmith [β42 (CD1)Phe-->Ser, TTT>TCT]. Hemoglobin 2012;36:161-5.
27. Li R, Wang T, Xie XM, Li DZ. Case report: prenatal diagnosis of Hb Hammersmith [β42(CD1)Phe-->Ser; HBB: c.128T > C] in a family with an adult male patient. Hemoglobin 2014;38: 142-5.
28. Takihara Y, Nakamura T, Yamada H, Takagi Y, Fukumaki YA. A novel mutation in the TATA box in a Japanese patient with beta+-thalassemia. Blood 1986;67:547-50.
29. 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.
30. Yamsri S, Singha K, Prajantasen T, Taweenan W, Fucharoen G, Sanchaisuriya K, et al. A large cohort of β(+)-thalassemia in Thailand: molecular, hematological and diagnostic considerations. Blood Cells Mol Dis 201;54:164-9.
31. Bardakdjian-Michau J, Fucharoen S, Delanoe-Garin J, Kister J, Lacombe C, Winichagoon P, et al. Hemoglobin Dhonburi alpha 2 beta 2 126 (H4) Val----Gly: a new unstable beta variant producing a beta-thalassemia intermedia phenotype in association with beta zero-thalassemia. Am J Hematol 1990;35:96-9.
32. Viprakasit V, Chinchang W. Two independent origins of Hb Dhonburi (Neapolis) [beta 126 (H4) Val-->Gly]: an electrophoretically silent hemoglobin variant. Clin Chim Acta 2007; 376:179-83.
33. Moghimi B, Yavarian M, Oberkanins C, Amini S, Khatami S, Rouhi S, et al. Hb Dhonburi (Neapolis) [beta126(H4)Val-->Gly] identified in a family from northern Iran. Hemoglobin 2004; 28:353-6.
34. Winichagoon P, Fucharoen S, Wilairat P, Chihara K, Fukumaki Y, Wasi P. Identification of five rare mutations including a novel frameshift mutation causing beta zerothalassemia in Thai patients with beta zero-thalassemia/hemoglobin E disease. Biochim Biophys Acta 1992;1139:280-6.
35. Hasan KN, Khaleque MA, Majumder AK, Rahman MM, Akhteruzzaman S. Identification of compound heterozygosity for a rare beta-globin gene mutation, codon 15 (-T) with a common mutation IVS1-5 (G>C) by direct sequencing in a Bangladeshi patient. Biores comm 2016;2:245–8.
36. Hernanda PY, Tursilowati L, Arkesteijn SG, Ugrasena ID, Larasati MC, Soeatmadji SM, et al. Towards a prevention program for β-thalassemia. The molecular spectrum in East Java, Indonesia. Hemoglobin 2012;36:1-6.
37. Gajra B, Bandyopadhyay D, Chakrabarti S, Sengupta B, De M, Shaji RV, et al. Thalassemia beta0 due to an identical frameshift mutation, codon 15 (-T) in both parents. Am J Hematol 2004;75:117.
38. Doro MG, Casu G, Frogheri L, Persico I, Triet LPM, Hoa PTT, et al. Molecular characterization of β-Thalassemia mutations in Central Vietnam. Hemoglobin 2017;41:96-9.
39. Boonyawat B, Monsereenusorn C, Traivaree C. Molecular analysis of beta-globin gene mutations among Thai betathalassemia children: results from a single center study. Appl Clin Genet 2014;7:253-8.
40. Girard JM, Drevin G, Brasme JF, Pissard S, Reynier P, Simard G, et al. Clinical and biological specificity of beta-thalassemia intermedia: a case report. Ann Biol Clin (Paris) 2016;74:688- 92.
2. 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.
3. Modell B. Epidemiological estimates for haemoglobin disorders: WHO South East Asian Region by Country. Bull World Health Organ [serial on the Internet]. 2007 [cited 2019 Oct 1]. Available from: http://www.modell-almanac.net/world. sear.pdf
4. Nopparatana C, Panich V, Saechan V, Sriroongrueng V, Nopparatana C, Rungjeadpha J, et al. The spectrum of betathalassemia mutations in southern Thailand. Southeast Asian J Trop Med Public Health 1995;26(Suppl 1):S229-34.
5. Sutcharitchan P, Saiki R, Fucharoen S, Winichagoon P, Erlich H, Embury SH. Reverse dot-blot detection of Thai betathalassaemia mutations. Br J Haematol 1995;90:809-16.
6. 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;71:109-13.
7. 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;48:137-44.
8. Cai SP, Zhang JZ, Doherty M, Kan YW. A new TATA box mutation detected at prenatal diagnosis for beta-thalassemia. Am J Hum Genet 1989;45:112-4.
9. Sanchaisuriya K, Fucharoen S, Fucharoen G, Ratanasiri T, Sanchaisuriya P, Changtrakul Y, et al. A reliable screening protocol for thalassemia and hemoglobinopathies in pregnancy: an alternative approach to electronic blood cell counting. Am J Clin Pathol 2005;123:113-8.
10. Kollia P, Gonzalez-Redondo JM, Stoming TA, Loukopoulos D, Politis C, Huisman TH. Frameshift codon 5 [Fsc-5 (-CT)] thalassemia; a novel mutation detected in a Greek patient. Hemoglobin 1989;13:597-604.
11. Agarwal S, Hattori Y, Agarwal SS. Rare beta-thalassemia mutations in Asian Indians. Am J Hematol 2000;65:322-3.
12. Akhavan-Niaki H, Derakhshandeh-Peykar P, Banihashemi A, Mostafazadeh A, Asghari B, Ahmadifard MR, et al. A comprehensive molecular characterization of beta-thalassemia in a highly heterogeneous population. Blood Cells Mol Dis 2011;47:29-32.
13. Zahed L. The Spectrum of beta-Thalassemia mutations in the Arab Populations. J Biomed Biotechnol 2001;1:129-32.
14. Zhang J, Zhu BS, He J, Zeng XH, Su J, Xu XH, et al. The spectrum of α- and β-thalassemia mutations in Yunnan province of Southwestern China. Hemoglobin 2012;36:464- 73.
15. Vidaud M, Gattoni R, Stevenin J, Vidaud D, Amselem S, Chibani J, et al. A 5' splice-region G----C mutation in exon 1 of the human beta-globin gene inhibits pre-mRNA splicing: a mechanism for beta+-thalassemia. Proc Natl Acad Sci U S A 1989;86:1041-5.
16. Gonzalez-Redondo JM, Stoming TA, Lanclos KD, Gu YC, Kutlar A, Kutlar F, et al. Clinical and genetic heterogeneity in black patients with homozygous beta-thalassemia from the southeastern United States. Blood 1988;72:1007-14.
17. Hamid M, Shariati G, Saberi A, Kaikhaei B, Galehdari H,Mohammadi-Anaei M. Identification of IVS-I (-1) (G > C) or Hb Monroe as a report on the beta-globin gene with a betathalassemia minor phenotype in south of Iran. Arch Iran Med 2013;16:563-4.
18. Piammongkol S, Chongsuvivatwong V, Williams G, Pornpatkul M. The prevalence and determinants of iron deficiency anemia in rural Thai-Muslim pregnant women in Pattani province. Southeast Asian J Trop Med Public Health 2006;37: 553-8.
19. Dacie JV, Shinton NK, Gaffney PJ Jr, Lehmann H. Haemoglobin Hammersmith (beta-42 (CDI) Phe replaced by ser). Nature 1967;216:663-5.
20. Akiyama M, Murayama S, Yokoi K, Yanagisawa T, Hattori Y, Yamashiro Y, et al. Hemoglobin Hammersmith [beta 42(CD1) Phe --> Ser] causing severe hemolytic anemia in a Japanese girl. Pediatr Blood Cancer 2006;47:839-41.
21. Rahbar S, Feagler RJ, Beutler E. Hemoglobin Hammersmith (beta 42 (CD1) Phe replaced by Ser) associated with severe hemolytic anemia. Hemoglobin 1981;5:97-105.
22. Cunningham TA, Baker F, Kobrinsky NL, Cepreganova B, Baysal E, Wilson JB, et al. The unstable Hb Hammersmith or alpha2 beta2(42)(CD1)Phe----Ser observed in an Indian child; identification by HPLC and by sequence analysis of amplified DNA. Hemoglobin 1992;16:19-25.
23. Rahbar S, Bennetts GA, Ettinger LJ. Hemoglobin Hammersmith as the cause of severe hemolytic anemia in a Chinese girl. Am J Pediatr Hematol Oncol 1986;8:13-7.
24. Tuohy AM , McKie VC, Sabio H, Kutlar F, Kutlar A, Wilson JB. Hb Hammersmith [beta 42(CD1) Phe-->Ser]: occurrence as a de novo mutation in black monozygotic twins with multiple congenital anomalies. J Pediatr Hematol Oncol 1998;20:563-6.
25. Sonati MF, Kimura EM, Abreu CF, Oliveira DM, Pinheiro VR, Costa FF. Hemoglobin Hammersmith [beta 42 (CD1) Phe --> Ser] in a Brazilian girl with congenital Heinz body hemolytic anemia. Pediatr Blood Cancer 2006;47:855-6.
26. Park S, Kang HJ, Cho SI, Kim SY, Seong MW, Park SS. A case report of a male patient with Hb Hammersmith [β42 (CD1)Phe-->Ser, TTT>TCT]. Hemoglobin 2012;36:161-5.
27. Li R, Wang T, Xie XM, Li DZ. Case report: prenatal diagnosis of Hb Hammersmith [β42(CD1)Phe-->Ser; HBB: c.128T > C] in a family with an adult male patient. Hemoglobin 2014;38: 142-5.
28. Takihara Y, Nakamura T, Yamada H, Takagi Y, Fukumaki YA. A novel mutation in the TATA box in a Japanese patient with beta+-thalassemia. Blood 1986;67:547-50.
29. 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.
30. Yamsri S, Singha K, Prajantasen T, Taweenan W, Fucharoen G, Sanchaisuriya K, et al. A large cohort of β(+)-thalassemia in Thailand: molecular, hematological and diagnostic considerations. Blood Cells Mol Dis 201;54:164-9.
31. Bardakdjian-Michau J, Fucharoen S, Delanoe-Garin J, Kister J, Lacombe C, Winichagoon P, et al. Hemoglobin Dhonburi alpha 2 beta 2 126 (H4) Val----Gly: a new unstable beta variant producing a beta-thalassemia intermedia phenotype in association with beta zero-thalassemia. Am J Hematol 1990;35:96-9.
32. Viprakasit V, Chinchang W. Two independent origins of Hb Dhonburi (Neapolis) [beta 126 (H4) Val-->Gly]: an electrophoretically silent hemoglobin variant. Clin Chim Acta 2007; 376:179-83.
33. Moghimi B, Yavarian M, Oberkanins C, Amini S, Khatami S, Rouhi S, et al. Hb Dhonburi (Neapolis) [beta126(H4)Val-->Gly] identified in a family from northern Iran. Hemoglobin 2004; 28:353-6.
34. Winichagoon P, Fucharoen S, Wilairat P, Chihara K, Fukumaki Y, Wasi P. Identification of five rare mutations including a novel frameshift mutation causing beta zerothalassemia in Thai patients with beta zero-thalassemia/hemoglobin E disease. Biochim Biophys Acta 1992;1139:280-6.
35. Hasan KN, Khaleque MA, Majumder AK, Rahman MM, Akhteruzzaman S. Identification of compound heterozygosity for a rare beta-globin gene mutation, codon 15 (-T) with a common mutation IVS1-5 (G>C) by direct sequencing in a Bangladeshi patient. Biores comm 2016;2:245–8.
36. Hernanda PY, Tursilowati L, Arkesteijn SG, Ugrasena ID, Larasati MC, Soeatmadji SM, et al. Towards a prevention program for β-thalassemia. The molecular spectrum in East Java, Indonesia. Hemoglobin 2012;36:1-6.
37. Gajra B, Bandyopadhyay D, Chakrabarti S, Sengupta B, De M, Shaji RV, et al. Thalassemia beta0 due to an identical frameshift mutation, codon 15 (-T) in both parents. Am J Hematol 2004;75:117.
38. Doro MG, Casu G, Frogheri L, Persico I, Triet LPM, Hoa PTT, et al. Molecular characterization of β-Thalassemia mutations in Central Vietnam. Hemoglobin 2017;41:96-9.
39. Boonyawat B, Monsereenusorn C, Traivaree C. Molecular analysis of beta-globin gene mutations among Thai betathalassemia children: results from a single center study. Appl Clin Genet 2014;7:253-8.
40. Girard JM, Drevin G, Brasme JF, Pissard S, Reynier P, Simard G, et al. Clinical and biological specificity of beta-thalassemia intermedia: a case report. Ann Biol Clin (Paris) 2016;74:688- 92.
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2020-05-15
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Srewaradachpisal K, Tepakhan W, Kanjanaopas S, Nopparatana C, Wongchanchailert M, Nopparatana C. Rare β-Globin Gene Mutations including a de novo Mutation of Hemoglobin Hammersmith in Southern Thailand. J Health Sci Med Res [Internet]. 2020 May 15 [cited 2024 Nov. 23];38(3):221-9. Available from: https://he01.tci-thaijo.org/index.php/jhsmr/article/view/244168
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