α-Thalassemia caused by an unstable α-globin mutant

Abstract

In a previous study, molecular cloning of the α-globin genes from a patient with nondeletion Hb-H disease (genotype ---/αα) showed that a single nucleotide mutation (CTG to CCG) in one of the genes resulted in a leucine to proline substitution. This paper describes the approach we used to detect the abnormal α-globin chain. The chain was identified using a cell-free translation system. It turned over rapidly both in vitro and in vivo in the patient's reticulocytes. The unusual feature of this unstable α-globin is that the α-globin deficiency causes α-thalassemia. Simple heterozygotes for this lesion (α(Pro)α/αα) resemble α-thalassemia carriers and do not exhibt the hemolytic anemia usually associated with unstable hemoglobins.