Thalassaemias and Other Haemoglobinopathies

  • John Old


The haemoglobinopathies are a heterogeneous group of autosomal recessive disorders caused by defects in the human globin genes. The disorders consist of the thalassaemias, characterised by either the reduced synthesis of one or more of the globin chains, and the haemoglobin variants, characterised by the synthesis of a structurally abnormal globin (Weatherall and Clegg, 2001). They form the most common single gene disorder in the world, and are found at high frequencies in many populations as a result of positive selection pressure due to falciparum malaria (see Chapter 24). Individuals with the carrier state are easily identifiable, permitting the control of the serious haemoglobinopathies by a programme of carrier screening, counselling and prenatal diagnosis (Petrou and Modell, 1995). The most important disorders for which prenatal diagnosis is considered are β°-thalassaemia, ß-thalassaemia, sickle cell anaemia and the various compound heterozygous states that result in a clinically significant disease.


Prenatal Diagnosis Globin Gene Thalassaemia Intermedium Abnormal Haemoglobin High Gene Frequency 
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  1. Abraham R, Thomas M, Britt R, Fisher C, Old J. (2003) Hb Q India: an uncommon variant diagnosed in three Punjabi patients with diabetes is identified by a novel DNA test. J Clin Pathol 56; 0–3CrossRefGoogle Scholar
  2. Agarwal S, Gulati R, Singh K. (1997) Hemoglobin E-beta thalassaemia in Uttar Pradesh. Indian Pediatr 34; 287–292.PubMedGoogle Scholar
  3. Agarwal S, Pradhab M, Gupta UR, Sarwai S, Agarwal SS. (2000) Geographic and ethnic distribution of beta thalassaemia mutations in Uttar Pradesh, India. Hemoglobin 24; 89–97PubMedCrossRefGoogle Scholar
  4. Ahmed S, Petrou M, Saleem M (1996) Characterisation of beta-thalassaemia mutations in Pakistan; A basis for prenatal diagnosis. British Journal of Haematology, 57, 476–482.Google Scholar
  5. Ahmed S, Saleem M, Sultana N, Raashid Y, Waqar A, Anwar M, Modell B, Karamat KA, Petrou M. (2000) Prenatal diagnosis of beta-thalassaemia in Pakistan: experience in a Muslim country. Prenatal Diagnosis 20: 378–383PubMedCrossRefGoogle Scholar
  6. Ajmani M, Sharma A,Talukder G, Bhattacharya DK (1976) Beta thalassaemia trait in West Bengal-a methodological study. Curr. Sci 45; 476Google Scholar
  7. Bandyopadhyay A, Bandyopadhyay S, Dasgupta Ub, Chandra S, Da MK. (2001) Detection of rare splice acceptor site mutation (IVSI nt 130 GoC) of the beta globin gene in 3 patients of Eastern India. Am J Haematol 67; 149–149CrossRefGoogle Scholar
  8. Baysal, E., Sharma, S., Wong, S.C., Jogessar, V.B. and Huisman, T.H.J. (1994) Distribution of 0-thalassemia mutations in three Asian Indian populations with distant geographical locations. Hemoglobin, 18, 201–209.PubMedCrossRefGoogle Scholar
  9. Bernini, L.F. and Harteveld, C.L. (1998) α-Thalassaemia. Clinical Haematology: Sickle Cell Disease and Thalassaemia (ed. by G. P. Rodgers) p. 53–90. Bailliere Tindall, London.Google Scholar
  10. Brittenham G, Lozoff B, Harris JW, Kan YW, Dozy AM, Nayudu NVS. (1980) Alpha globin gene number: population and restriction enzyme studies. Blood 55; 706–708PubMedGoogle Scholar
  11. Brittenham GM. (1981) Hemoglobinopathies in India. Hemoglobin 5; 751–766.PubMedCrossRefGoogle Scholar
  12. Cürük, M.A., Baysal, E., Gupta, R.B. Huisman THJ (1993) An IVS-I-117 (GoA) acceptor splice site mutation in the 01-globin gene is a nondeletional β-thalassaemia-2 determinant in an Indian population. British Journal of Haematology, 85, 148–152.PubMedCrossRefGoogle Scholar
  13. Dastidar DG, Dutta RN, Gupta P, Old J. (1994) detection of beta thalassaemia mutations in eastern Indian population by polymerase chain reaction. Indian J Med Res 100; 111–114Google Scholar
  14. De M, Das SK, Bhattacharya DK, Talukder G. (1997) The occurrence of beta thalassaemia mutations and its interaction with hemoglobin E in the eastern India. Int J Hematol 66; 31–37CrossRefGoogle Scholar
  15. De Jong W.W., Khan P.M. and Bernini L.F. (1975) Hemoglobin Koya Dora: high frequency of a chain termination mutant. Am. J. Hum. Gen. 27, 81–90Google Scholar
  16. De Silva S, Fisher CA, Premawardhena A, Lamabadusuriya Sp, Peto TEA, Perera G, Old JM, Clegg JB, Olivieri NF, Weatherall DJ and the Sri Lanka Thalassaemia Study Group. (2000) Thalassaemia in Sri Lanka: implications for the future health burden of Asian populations. Lancet 355; 786–791CrossRefGoogle Scholar
  17. Desai S, Cohal R, Gupte S, Mohanty D (1997) Is cellulose acetate electrophoresis a suitable technique for detection of Hb Bart’s at birth? Hum Hered. 47; 181–184PubMedCrossRefGoogle Scholar
  18. Drysdale HC and Higgs DR. (1988) β-thalassaemia in an Asian Indian. Br. J. Haematol 68; 264–264PubMedCrossRefGoogle Scholar
  19. Embury, S.H., Miller, J.A., Dozy, A.M., Kan, Y.W., Chan, V. and Todd, D. (1980) Two different molecular organizations account for the single Į-globin gene of the Įthalassaemia-2 genotype. Journal of Clinical Investigation, 66, 1319–1325PubMedCrossRefGoogle Scholar
  20. Fodde R, Losekoot M, van den Broek MN, Oldenburg M, Rashida N, Schreuder A, Wijnen JT, Giordano PC, Nayudu NV, Khan PM (1991) Prevalence and molecular heterogeneity of alpha thalassaemia in two tribal populations from Andhra Pradesh, India. Hum Genet 80; 157–160CrossRefGoogle Scholar
  21. Furuumi H, Firdous N, Inoue T, Ohta H, Winichagoon P, Fucharoen, Fukumaki Y. (1998) Molecular basis of beta-thalassaemia in the Maldives. Hemoglobin 22; 141–151PubMedCrossRefGoogle Scholar
  22. Gilman JG, Brinson EC, Mishima N. (1992). The 32.6 kb Indian β-thlassaemia deletion ends in a 3.4 kb L1 element downstream of the β-globin gene. Br. J. Haematol. 82; 417–421.PubMedCrossRefGoogle Scholar
  23. Gorakshakar AC, Lulla CP, Nadkarni AH, Paear AR, Desai SN, Colah, RB, Mohanty D. (1997) Prenatal diagnosis of beta-thalassaemia among Indians using denaturing gradient gel electrophoresis. Hemoglobin 21: 421–435PubMedCrossRefGoogle Scholar
  24. Gupta RB, Tiwary RS, Pande Pl, Kutlar F, Oner C, Oner R, Huisman TH. (1991) Hemoglobinopathies among the Gond tribal groups of Central India; interaction of β- and β-thalassaemia with β chain variants. Hemoglobin 15; 441–458PubMedCrossRefGoogle Scholar
  25. Gupta A, Hattori Y, Agarwal S. (2002) Initiation mutation in an Asian Indian family. Am J Haematol 71; 134–136CrossRefGoogle Scholar
  26. Harkness, M., Harkness, D.R., Kutlar, F., Kutlar, A., Wilson, J.B., Webber, B.B., Codrington, J.F. and Huisman, T.H.J. (1990) Hb Sun Prairie or α-2130(H13)Ala—Pro-β-2: a new unstable variant occurring in low quantities. Hemoglobin, 14, 479–490.PubMedCrossRefGoogle Scholar
  27. Harteveld, C.L., Losekoot, M., Haak, H., Heister, G.A., Giordano, P.C. and Bernini, L.F. (1994) A novel polyadenylation signal mutation in the Į2-globin gene causing Į thalassaemia. British Journal of Haematology, 87, 139–143.PubMedCrossRefGoogle Scholar
  28. Harteveld, C.L., van Delft P, Wijermans PW Kappers-Klunne MC, Weegenaar J, Losekoot, M., Giordano, P.C. (2003) A novel 7.9 kb deletion causing Į+-thalassaemia in two independent families of Indian origin Br J Haemat 120; 364–366.CrossRefGoogle Scholar
  29. Hassal OW, Tillyer ML, Old JM. (1998) Prevalence and molecular basis of alpha thalassaemia in British South Asians. J Med Screen. 5; 31–33Google Scholar
  30. Henthorn PS, Mager DK, Huisman THJ, Smithies O. (1986). A gene deletion ending within a complex array of repeated sequences 3’ to the human beta globin gene cluster. Proc. Natl. Acad. Sci. USA. 83; 5194–5198.PubMedCrossRefGoogle Scholar
  31. Higgs DR, Aldridge BE, Lamb J, Clegg JB, Weatherall DJ, Hayes RJ, Grandiso Y, Lowrie Y, Mason KP, Serjeant BE, Serjeant GR. (1982) The interaction of alpha-thalassemia and homozygous sickle-cell disease. New England Journal of Medicine; 306: 1441–1446.PubMedCrossRefGoogle Scholar
  32. Huisman, T. H. J., Carver, M. F. H. and Baysal, E. (Eds.) A Syallabus of Thalassemia Mutations. The Sickle Cell Anemia Foundation, Augusta, GA, USA, 1997.Google Scholar
  33. Hundrieser j, Deka R, Gogol BC (1998). B-globin gene associated DNA haplotypes and frameworks in the Karachi population of Assam (India). Human Heredity, 38; 240–245CrossRefGoogle Scholar
  34. Jennings MW, Jones RW, Wood WG, Weatherall DJ. (1985). Analysis of an inversion within the human beta globin gene cluster. Nucl. Acids Res. 13; 2897–2906.PubMedCrossRefGoogle Scholar
  35. Jones RW, Old JM, Trent RJ, CleggJB, Weatherall DJ (1981). Major rearrangement in the human beta-globin gene cluster. Nature, 291: 39–44.PubMedCrossRefGoogle Scholar
  36. Kennedy KAR. (1981) Skeletal biology: when bones tell tales. Archeology 34; 17–24Google Scholar
  37. Khan, S. N. and Riazuddin, S. (1998) Molecular characterisation of β-thalassaemia in Pakistan. Hemoglobin, 22: 333–345PubMedCrossRefGoogle Scholar
  38. Khan SN, Butt FI, Riazuddin S, Galanello R. (2000) Hb Sallanches [alpha104(G11)Cys—Tyr]: a rare alpha 2-globin chain variant found in the homozygous state in three members of a Pakistani family. Hemoglobin 24; 31–35PubMedCrossRefGoogle Scholar
  39. Khan, S. N., Riazuddin, S. and Galanello, R. (2000). Identification of three rare β-thalassaemia mutations in the Pakistan population. Hemoglobin, 24: 15–22PubMedCrossRefGoogle Scholar
  40. Kotea N, Baligadoo S, Surran SK, Ramasawmy R, Lu CY, Ducrocq R, Labie D, Krishnamoorthy R, Nagel R. (1995). Bicentric origin of sickle hemoglobin among the inhabitants of Mauritius Island. Blood, 86; 407–408PubMedGoogle Scholar
  41. Kotea, N., Ramsawawmy, R., Lu, C. Y., Fa, N. S., Gerard, N., Beesoon, S., Ducrocq, R., Surran, S. K., Nagel, R. L. and Krishnamoorthy, R. (2000) Spectrum of beta thalassaemia mutations and their linkage to beta-globin gene haplotypes in the Indo-Mauritians. Am. J. Hematol., 63: 11–15PubMedCrossRefGoogle Scholar
  42. Kukreti R, Dash D, Vineetha KE, Chakravarty S, Das SK, De M, Talukder G. (2002) Spectrum of beta thalassaemia mutations and their association with allele sequence polymorphisms at the beta globin gene cluster in an eastern Indian population. Am J Haematol 70; 269–377.CrossRefGoogle Scholar
  43. Kulozik AE, Wainscoat JS, Serjeant GR, Kar BC, Al-Awamy B, Essan GJ, Falusi AG, Haque SK, Hilali AM, Kate S. (1986) Geographical survey of α-globin gene haplotypes: Evidence for an independent Asian origin of the sickle-cell mutation. American Journal of Human Genetics;39:239–244.Google Scholar
  44. Kulozik, A.E., Kar, B.C., Serjeant, B.E. and Weatherall, D.J. (1988) The molecular basis of Įthalassaemia in India; its interaction with the sickle gene. Blood, 71, 467–472.PubMedGoogle Scholar
  45. Kutlar A, Gardiner MB, Headlee, MG, Reese Al, Cleek MP, Nagle S, Sukumaran PK, Huisman THJ. (1984) Heterogeneity in the molecular basis of three types of hereditary persistence of fetal hemoglobin and the relative synthesis of the Gγ and Aγ types of chains. Bichem Genet 22; 21–35.CrossRefGoogle Scholar
  46. Labie D Srinivas R, Dunda O, Dode C, Lapoumeroulie C, Devi V, Devi S, Ramasami K, Elion J, Ducrocq R. (1989) Haplotypes in tribal Indians bearing the sickle gene:evidence for the unicentric origin of the βs mutation and the unicentric origin of the tribal populations of India. Hum Biol 61; 479–491.PubMedGoogle Scholar
  47. Lehman H and Cutbush M. (1952) Sickle-cell trait in Southern India. Br. Med. J. 1; 289–290.CrossRefGoogle Scholar
  48. Livingstone FB. (1985) Frequencies of hemoglobin variants. Oxford University Press New YorkGoogle Scholar
  49. Livingstone FB. (1989) Who gave who hemoglobin S: the use of restriction site haplotype variation for the interpretation of the evolution of the βS-globin gene. Am. J Hum Biol. 1; 289–302CrossRefGoogle Scholar
  50. Madan N, Sharma S, Rusia U, Sen S, Sood SK. (1998) Beta thalassaaemia mutations in northern India (Delhi). Indian J Med Res 107; 134–141PubMedGoogle Scholar
  51. Mishima N, Landman H, Huisman THJ, Gilman JG. (1989). The DNA deletion in an Indian β-thalassaemia begins one kilobase from the Aγ-globin gene and ends in a L1 repetitive sequence. Br. J. Haematol. 73; 375–379PubMedCrossRefGoogle Scholar
  52. Modell BC and Petrou M (1983) The problem of haemoglobinopathies in India. Indian Journal of Haematology. 1; 5–16.Google Scholar
  53. Modiano G, Morpurgo G, Terranato L Novelletto A, Di Renzo A, Colombo B, Purpura, Mariani M, Sentachiara-Benerecetti S, Brega A. (1991) Protection against malaria morbidity: near fixation of the α-thalassaemia gene in a Nepalese population. Am J Hum Genet 48; 390–397PubMedGoogle Scholar
  54. Mukherjee MB, Lu CY, Ducrocq R, Gangakhedkar RR, Colah RB, Kadam MD, Mohanty D, Nagel RL, Krishnamoorthy R. (1997) Effect of alpha-thalassaemia on sickle-cell anemia linked to the Arab-Indian haplotype in India. Am J Haematol 55; 104–109.CrossRefGoogle Scholar
  55. Nadkarni A, Sakaguchi T, Takaku H, Gorakshakar A, Phanasgaonk SA, Colah RB, Mohanty D, Kiyama R. (2002) A novel beta0-thalassaemia mutation at codon 55 (-A) and a rare 17 bp deletion at codons 126–131 in the Indian population. Hemoglobin 26; 41–47PubMedCrossRefGoogle Scholar
  56. Old JM, Varawalla NY and Weatherall DJ(1990). Rapid detection and prenatal diagnosis of β-thalassaemia: studies in the Indian and Cypriot populations in the UK. Lancet, 336; 834–837Google Scholar
  57. Old J (1996) Haemoglobinopathies. Prenat. Diag. 16, 1181–1186CrossRefGoogle Scholar
  58. Old, J., Khan, S., Verma, I., Fucharoen, S., Kleanthous, M., Ioannou, P., Kotea, N., Fisher, C., Sheikh, R., Saxena, R., Winichagoon, P., Kyriacou, K., Quobaili, F.A. and Khan, B. (200 1) A multi-centre study in order to define further the molecular basis of β-thalassemia in Thailand, Pakistan, Sri Lanka, Mauritius, Syria, and India, and to development a simple molecular diagnostic strategy by ARMS-PCR. Hemoglobin, 25; 397–407Google Scholar
  59. Parikh P, Cotton M, Boehm C, Kazazian HH Jr. (1990) Ethnic distribution of betathalassaemia in the Indian subcontinent. Lancet 336; 1006–1006PubMedCrossRefGoogle Scholar
  60. Petrou, M. and Modell, B. (1995) Prenatal screening for haemoglobin disorders. Prenatal. Diagnosis. 15, 1275–1295PubMedCrossRefGoogle Scholar
  61. Powars DR. (1991) βs-gene cluster haplotypes in sickle cell anemia. Hematology/Oncology Clinics of North America;5:475–493.Google Scholar
  62. Prehu MO, Prehu C, Goossens M, Galacteros E, Wajcman H. (1994) A new anti-Lepore hemoglobin Hb P India (β87-δ105), found in coincidence with a CMG substitution at position 162 of IVS2 in both the δ and δβ genes, questions on the genetic mechanisms leading to Hbs Lepore and anti-Lepore. Blood 83; 261aGoogle Scholar
  63. Reddy PH, Petrou M, Reddy PA, Tiurory RS, Modell B (1995) Hereditary anaemias and iron deficiency in a tribal population (the Baiga) of central India. Eur. J Haematol 55, 103–109PubMedCrossRefGoogle Scholar
  64. Saxena R, Thomas E, Verma IC (1998) Detection of beta-thalassaemia mutation insertion ATCT at codon 47/48 by ARMS technique for screening and prenatal diagnosis. Ind J Med Res 105; 275–277Google Scholar
  65. Saxena R, Jain PK, Thomas E, Verma IC (1998) Prenatal diagnosis of beta-thalassaemia: experience in a developing country. Prenatal Diagnosis 18: 1–7PubMedCrossRefGoogle Scholar
  66. Saxena R, Moi L, Demurtas M, Rosatelli MC, Cao A, Verma IC (2000) A beta-thalassaemia allele with 3 base substitutions in codons 4/5 and 6 (ACT CCT GAG—)-ACA TCT TAG) detected by denaturing gradient gel electrophoresis and sequencing. Indian J Med Res 111; 24–27PubMedGoogle Scholar
  67. Shaji RV, Gerard N, Krishnamoorthy R, Srivastava A, Chandy M. (2002a) Co-existence of a novel beta-globin gene deletion (codons 81–8) with the codon 30 (GEC) mutation in an Indian patient with beta0-thlassaemia. Hemoglobin 26; 49–57PubMedCrossRefGoogle Scholar
  68. Shaji RV, Srivastava A, Krishnamoorthy R, Chandy M. (2002b) A novel beta-thalassaemia mutation in an Asian Indian. Hemoglobin 26; 237–243PubMedCrossRefGoogle Scholar
  69. Thakur (Mahadik) C, Vaz F, Bannerjee M, Kapadia C, Natrajan PG, Yagnik H, Gangal S (2000) Prenatal diagnosis of beta-thalassaemia and other haemoglobinopathies in India. Prenatal Diagnosis 20: 194–201CrossRefGoogle Scholar
  70. Thein, S.L., Hesketh, C., Wallace, R.B. and Weatherall, D.J. (1988) The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: Application to prenatal diagnosis. British Journal of Haematology, 70, 225–232.PubMedCrossRefGoogle Scholar
  71. Vandenplas, S., Higgs, D.R., Nicholls, R.D., Bester, A.J. and Mathew, C.G.P. (1987) Characterization of a new α° thalassaemia defect in the South African population. British Journal of Haematology, 66, 539–542.PubMedCrossRefGoogle Scholar
  72. Varawalla, N. Y., Old, J. M. and Weatherall, D. J.(1991 a) Rare β-thalassaemia mutations in Asian Indians. Brit. J.Haemat., 79: 640–644Google Scholar
  73. Varawalla, N. Y., Old, J. M., Sarkar, R., Venkatesan, R. and Weatherall, D. J. (1991b). The spectrum of β thalassemia mutations on the Indian subcontinent: the basis for prenatal diagnosis. Brit. J. Haemat., 78: 242–247PubMedCrossRefGoogle Scholar
  74. Venkatesan R, Sarkar R, Old JM. (1992) ß-thalassaemia mutations and their linkage to β-haplotypes in tamil Nadu in Southern India. Clin Genet 42; 251–256PubMedCrossRefGoogle Scholar
  75. Verma, I.C., Saxena, R., Thomas, E. and Jain, P.K. (1997) Regional distribution of ß-thalassemia mutations in India. Human Genetics, 100; 109–113.PubMedCrossRefGoogle Scholar
  76. Wainscoat JS, Old J,M, Wood WG, Trent RJ, Weatherall DJ. (1984) Characterisation of an Indian (6ß)° thalassaemia. Br. J. Haematol 58: 353–360PubMedCrossRefGoogle Scholar
  77. Weatherall DJ, Clegg JB (Eds.). The Thalassemia Syndromes. (4th ed.) Blackwell Scientific Publications, Oxford, 2001Google Scholar

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  • John Old

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