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- (G gamma- and A gamma-) 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 gamma-mRNA level in compound heterozygotes. A significant discrepancy between Hb F and gamma-mRNA levels, observed in previously published studies, was confirmed indicating a less efficient gamma-mRNA translation. When the two different gamma-mRNA (G gamma- and A gamma-) levels were determined it was observed that in beta-thalassemia heterozygotes the extra gamma-mRNA was primarily of the G gamma type suggesting a more efficient translation of the A gamma-mRNA. This difference disappeared in homozygotes and compound heterozygotes: both mRNAs (G gamma- and A gamma-) translate with an equal efficiency.