The molecular basis for phenotypic variability of the common thalassaemias

The thalassaemias, the commonest monogenic diseases in humans, and the first to be analysed at the molecular level, show remarkable phenotypic heterogeneity. As much of this variability can be ascribed to acquired pathology resulting from complications of the profound anaemia that accompanies these diseases, it is often difficult to define the precise relationships between different mutations and their clinical manifestations. Some progress has been made, however. In this article, what has been learnt about genotype/phenotype relationships for the two common forms of thalassaemia is summarized.