Molecular Pathology of the Thalassaemia Syndromes

  • S. L. Thein
Part of the Developments in Hematology and Immunology book series (DIHI, volume 30)


The thalassaemiasare a heterogeneous group of inherited haemoglobin disorders characterizedby a reduced output or absence of one or more of the globin chains. The common forms α- and β-thalassaemias, are among the most common genetic disorders in the world. There is increasing evidence that heterozygotes for thalassaemia are protected from the severe effects of falciparum malaria, this selective advantage has greatly increased the gene frequencies of many thalassaemia alleles throughout the tropical and sub-tropical regions [1]. Both α- and β-thalassaemiashow a wide spectrum of clinical phenotypes ranging from severe anaemia and transfusion dependency in the homozygotes and compound heterozygotes to extremely mild forms which are clinically and haematologically silent, the so-called “silent” carrier states [2]. Furthermore, because the thalassaemias exist at a high frequency with the haemoglobin variants like Hb S, E and C in many populations, individuals may inherit more than one type giving rise to an extremely complex spectrum of clinical phenotypes. As the molecular pathology of the thalassaemiasare being characterized, it has become possible to relate these heterozygous clinical phenotypes to the underlying genotypes.


Globin Gene Globin Chain Ineffective Erythropoiesis Thalassaemia Syndrome Chain Imbalance 
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  1. 1.
    Flint J, Hill AVS, Bowden DK, et al. High frequencies of α thalassaemia are the result of natural selection by malaria. Nature 1986;321:744–49.PubMedCrossRefGoogle Scholar
  2. 2.
    Weatherall DJ, Clegg JB. The thalassaemia syndromes. Oxford: Blackwell Scientific 1981.Google Scholar
  3. 3.
    Stamatoyannopoulos G, Nienhuis AW. Hemoglobin switching. In: Stamatoyannopoulos G, Nienhuis AW, Majerus PW, Varmus H (eds). The molecular basis of blood diseases (2nd ed). Philadelphia: W.B. Saunders and Co. 1994:107–55.Google Scholar
  4. 4.
    Grosveld F, Dillon N, Higgs D. The regulation of human globin gene expressio. In: Higgs DR, Weatherall DJ (eds). The haemaglobinopathies. Baillière’s Clinical Haematology. London: Baillière Tindall 1993:31–55.Google Scholar
  5. 5.
    Higgs DR, Wood WG, Jarman AP, et al. A major positive regulatory region located far upstream of the human α globin gene locus. Genes Dev 1990;4:1588–601.PubMedCrossRefGoogle Scholar
  6. 6.
    Orkin SH. Globin gene regulation and switching: Circa 1990. Cell 1990;63: 665–72.PubMedCrossRefGoogle Scholar
  7. 7.
    Andrews NC, Orkin SH. Transcriptional control of erythropoiesis. Current Opinion in Hematology 1994;1:119–24.PubMedGoogle Scholar
  8. 8.
    Huisman THJ. The βand δ-thalassemia repository. Hemoglobin 1992;16:237–58.PubMedCrossRefGoogle Scholar
  9. 9.
    Thein SL. β-thalassaemia. In: Higgs DR, Weatherall DJ (eds). The haemoglobinopathies. Baillière’s Clinical Haematology. London: Baillière Tindall 1993:151–76.Google Scholar
  10. 10.
    Kazazian HHJ, Boehm CD. Molecular basis and prenatal diagnosis of β-thalassemia. Blood 1988;72:1107–16.PubMedGoogle Scholar
  11. 11.
    Gonzalez-Redondo JM, Stoming TA, Kutlar A, et al. A C→T substitution at nt-101 in a conserved DNA sequence of the promoter region of the β globin gene is associated with “silent” β-thalassemia. Blood 1989;73:1705–11.PubMedGoogle Scholar
  12. 12.
    Wong C, Dowling CE, Saiki RK, Higuchi RG, Erlich HA, Kazazian HHJ. Characterization of β-thalassaemia mutations using direct genomic sequencing of amplified single copy DNA. Nature 1987;330:384–86.PubMedCrossRefGoogle Scholar
  13. 13.
    Thein SL. Dominant β-thalassaemia: Molecular basis and pathophysiology. Brit J Haemat 1992;80:273–77.PubMedCrossRefGoogle Scholar
  14. 14.
    Thein SL, Wood WG, Wickramasinghe SN, Galvin MC. β-thalassemia unlinked to the β globin gene in an English family. Blood 1993;82:961–67.PubMedGoogle Scholar
  15. 15.
    Higgs DR. α thalassaemia. In: Higgs DR, Weatherall DJ (eds). The haemoglobinopathies. Baillière’s Clinical Haematology. London: Baillière Tindal 1993:117–50.Google Scholar
  16. 16.
    Higgs DR, Wood WG, Barton C, Weatherall DJ. Clinical features and molecular analysis of acquired HbH disease. Am J Med 1983;75:181–92.PubMedCrossRefGoogle Scholar
  17. 17.
    Wilkie AOM, Buckle VJ, Harris PC, et al. Clinical features and molecular analysis of the α. thalassemia/mental retardation syndromes. I. Cases due to deletions involving chromosome band 16p13.3. Am J Hum Genet 1990a;46:1112–26.PubMedGoogle Scholar
  18. 18.
    Wilkie AOM, Zeitlin HC, Lindenbaum RH, et al. Clinical features and molecular analysis of the α thalassemia/mental retardation syndromes. II. Cases without detectable abnormality of the α globin complex. Am J Hum Genet 1990b;46:1127–40.PubMedGoogle Scholar
  19. 19.
    Gibbons RJ, Suthers GK, Wilkie AOM, Buckle VJ, Higgs DR. X-linked α thalassemia/mental retardation (ATR-X) syndrome; localization to Xq12-q21.31 by X inactivation and linkage analysis. Am J Hum Genet 1992;51:1136–49.PubMedGoogle Scholar

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© Springer Science+Business Media Dordrecht 1995

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  • S. L. Thein

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