An Attempt at Demonstrating the Existence of a Nonsense Mutation in beta-Thalassemia

The authors have investigated the possibility that the Ferrara type of β-thalassemia, in which β-globulin synthesis is absent, may be due to a nonsense mutation on the gene for β-globin. This hypothesis has been tested by trying to detect the presence of newly synthesized β-globin fragments in the reticulocytes of homozygous β-thalassemic subjects. The red blood cells were incubated with [3H]leucine. The whole hemolysate was hydrolyzed with trypsin and several β-chain peptides were isolated by column chromatography and assayed for radioactivity. No incorporation of radioactive leucine could be detected in the various β-globin peptides isolated and examined. The hypothesis that a nonsense mutation is responsible for the absence of β-globin synthesis in the Ferrara β-thalassemia is not supported by these findings.