A novel globin structural mutant, Showa-Yakushiji (beta 110 Leu-Pro) causing a beta-thalassemia phenotype

Abstract

Molecular analysis of the beta-globin genes from a patient with a beta-thalassemia phenotype showed that a single nucleotide mutation (CTG-CCG) at codon 110 in one of the genes resulted in a leucine to proline substitution. The same mutation with a similar phenotype, was observed in her mother and sister, by Southern blotting analysis of DNAs digested with Mspl, the recognition site of which was created by this base substitution. This indicates a close relationship between this mutation and the beta-thalassemia phenotype. No anomalous peak of radioactivity was detected by reverse-phase high-performance liquid chromatography (HPLC) in the patient's reticulocytes incubated with isotopically labeled amino acid. The leucine-proline (Leu-Pro) substitution probably disrupts the G-helix and in turn interferes with globin contact points. The uncombined beta-globin chain would be rapidly destroyed and the beta-thalassemia phenotype would follow.