Molecular Pathology of the Thalassaemia Syndromes

Abstract

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.