Gene regulation and deregulation: a β globin perspective

The study of the β globin gene has provided great insights into the mechanisms of gene regulation and expression. In this review, we consider the normal regulation and expression of the β globin gene and illustrate how the various steps may be affected, providing a basis for understanding the molecular pathophysiology of β thalassemia. Mutations causing β thalassemia can be classified as β° or β+according to whether they abolish or reduce the production of β globin chains. The vast majority of β thalassemia is caused by point mutations, mostly single base substitutions, within the gene or its immediate flanking sequences. Rarely, β thalassemia is caused by major deletions of the β globin cluster. All these mutations behave as alleles of the β locus but in several families the β thalassemia phenotype segregates independently of the β globin complex, and are likely to be caused by mutations in trans -acting regulatory factors.