The αβ- andα2α1-globin mRNA ratios in different forms of α-thalassemia

AbstractThe present study provides information about the αβandα2α1-mRNA ratios in reticulocytes of normal adults and with different α-globin gene deficiencies; it found its origin in analytical data of blood samples from a Laotian couple and their newborn baby. The father carried the 4.2 kb deletion on one chromosome and a TAA → CAA mutation at the terminating codon of the α2 gene (Hb Constant Spring or CS) on the other chromosome. The mother had the 3.7 kb deletion on one chromosome and a TA A → TAT mutation at the terminating codon of the α2-globin gene (Hb Paksé) of the second chromosome. The baby was a compound heterozygote for the two termination codon mutations. The mRNA data for this family were compared to those for persons with several well-defined α-globin gene deficiencies. The results confirm the importance of the α2α1-mRNA for the synthesis of α chains in α-thalassemia-2 homozygotes (−α−α) and in patients with Hb H disease due to the deletion of three α-globin genes (−α−−). Furthermore, the mRNA production of the α1-globin gene on the chromosome with the αCS mutation (αCSα) is only one-half of that by the α2α1-globin gene of a chromosome with a 3.7 or 4.2 kb deletion, explaining the greater severity of, and higher Hb H level in Hb H patients with the αCSα condition (αCSα−−) as compared to those with the three gene deletion (−α−−). The methodology could be useful as a screening for the presence of point mutations leading to the functional loss of a single α-globin gene, provided common deletional alleles have been excluded