The alpha / beta and alpha 2 / alpha 1-globin mRNA ratios in different forms of alpha-thalassemia.

Abstract The present study provides information about the α β and α2 α1 - 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 T AA → C AA 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 → TA T mutation at the terminating codon of the α2-globin gene (Hb Pakse) 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 α CS mutation ( α CS α ) 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 α CS α condition ( α CS α −− ) 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.