Molecular defects in β-thalassemia

Reduced synthesis of structurally normal β-globin, the characteristic phenotype of genetic mutations which cause β-thalassemia, reflects a quantitative deficiency of β-globin mRNA in patients who have these mutations. Accumulation of globin mRNA in normal erythroid cells is dependent on a relatively high level of transcription of the globin genes, efficient processing of the globin mRNA precursors, and marked stability of the mature globin mRNAs; mutations which affect any of these processes can cause a quantitative deficiency of globin mRNA. In this paper, we review the approaches which we have taken to define the mutations which cause β-thalassemia.