The polyadenylation site mutation in the α-globin gene cluster

Abstract

In a previous study, we described a form of nondeletion α-thalassemia (α(T Saudi)α) found in subjects of Saudi Arabian origin. In the current study, using synthetic oligoprobe hybridization and restriction enzyme analysis, we have demonstrated that the molecular basis of α(T Saudi)α is due solely to a single base mutation (AATAAA → AATAAG) in the polyadenylation signal of the α2 gene and that the frameshift mutation in codon 14 of the linked α1 gene is the result of a cloning artefact. The α2 polyadenylation signal mutation occurs in other Middle Eastern and the Mediterranean populations and is responsible for the clinical phenotype of Hb H disease in some Saudi Arabian individuals with five α genes (α(T Saudi)α/(ααα)(T Saudi)). Evidence suggests that the (ααα)(T Saudi) haplotype has arisen as a result of a recombination between two misaligned chromosomes bearing the α(T Saudi)α defect.