alpha-, beta-, and gamma-mRNA levels in beta-thalassemia; Transcriptional and translational differences in heterozygotes, homozygotes, and compound heterozygotes

We have determined the relative levels of alpha-, beta-, and gamma- (Y-G- and Y-A-) mRNAs in the reticulocytes of patients with mild beta-thalassemia intermedia due to combinations of promoter mutations and a classical type of beta-thalassemia, as well as in their relatives. The expected differences in the alpha/beta-mRNA ratio confirmed the mild suppression of beta-mRNA synthesis, particularly in heterozygotes for the -101 (C-->T) promoter mutation and the large increase in the relative y-mRNA level in compound heterozygotes. A significant discrepancy between Hb F and y-mRNA levels, observed in previously published studies, was confirmed indicating a less efficient y-mRNA translation. When the two different y-mRNA (Y-G- and Y-A-) levels were determined it was observed that in beta-thalassemia heterozygotes the extra y-mRNA was primarily of the Y-G type suggesting a more efficient translation of the Y-A-mRNA. This difference disappeared in homozygotes and compound heterozygotes. both mRNAs (Y-G- and Y-A-) translate with an equal efficiency.