Beta-thalassaemia prototype of a single gene disorder with multiple phenotypes

Abstract

As the defective genes for more and more genetic disorders become unravelled, it is clear that patients with the same genotype can have many different clinical conditions even in monogenic disorders. The remarkable phenotypic diversity of the beta thalassaemias is prototypical of how the wide spectrum in disease severity can be generated. The most reliable and predictive factor of disease phenotype is the nature of the mutation at the beta-globin locus itself. However, relating phenotype to genotype is complicated by the complex interaction of the environment and other genetic factors at the secondary and tertiary levels, some implicated, and others, as yet unidentified. This article reviews the clinical and haematological diversity encountered in beta thalassaemia and their relationship with the underlying genotypes.