Molecular pathology of alpha-thalassemia.

The different classes of mutations found in the alpha- and beta-thalassemia syndromes are summarized in FIGURE 5. Mutations affecting almost every stage of globin gene expression have been described. The only lesion not yet characterized is one affecting enhancing sequences, although such sequences have not yet been identified in the globin gene system. The clinically important alpha-thalassemias are the deletion types, which occur with much higher frequency than the nondeletion lesions. In contrast, apart from one deletion beta-thalassemia lesion found in Pakistan, all the clinically significant beta-thalassemia lesions are not caused by gene deletion. The common beta-thalassemia lesions in the Mediterranean region and Asia are caused by defective mRNA synthesis, processing, or translation. Why deletion lesions predominate in the alpha-thalassemias and nondeletion ones in the beta-thalassemias remains an enigma.