The Molecular Basis of β-Thalassemia

The beta-thalassemias are characterized by a quantitative deficiency of beta-globin chains under-laid by a striking heterogeneity of molecular defects. Although most of the molecular lesions involve the structural beta gene directly, some down-regulate the gene through distal cis effects, and rare trans-acting mutations have also been identified. Most beta-thalassemias are inherited in a Mendelian recessive fashion but there is a subgroup of beta-thalassemia alleles that behave as dominant negatives. Unraveling the molecular basis of beta-thalassemia has provided a paradigm for understanding of much of human genetics.