α-, β-, and y-mRNA Levels in β-Thalassemia; Transcriptional and Translational Differences in Heterozygotes, Homozygotes, and Compound Heterozygotes

Abstract

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