THE ALPHA BETA-GLOBIN AND ALPHA-2/ALPHA-1-GLOBIN MESSENGER-RNA RATIOSIN DIFFERENT FORMS OF ALPHA-THALASSEMIA/

The present study provides information about the alpha/beta and alpha 2/alpha 1-mRNA ratios in reticulocytes of normal adults and individual s with different alpha-globin gene deficiencies; it found its origin i n analytical data of blood samples from a Laotian couple and their new born baby. The father carried the 4.2 kb deletion on one chromosome an d a TAA --> CAA mutation at the terminating codon of the alpha 2 gene (Hb Constant Spring or CS) on the other chromosome. The mother had the 3.7 kb deletion on one chromosome and a TAA --> TAT mutation at the t erminating codon of the alpha 2-globin gene (Hb Pakse) of the second c hromosome, The baby was a compound heterozygote for the two terminatio n codon mutations. The mRNA data for this family were compared to thos e for persons with several well-defined alpha-globin gene deficiencies . The results confirm the importance of the alpha 2 alpha 1-mRNA for t he synthesis of a chains in alpha-thalassemia-2 homozygotes (-alpha/-a lpha) and in patients with Hb H disease due to the deletion of three a lpha-globin genes (-alpha/--). Furthermore, the mRNA production of the alpha 1-globin gene on the chromosome with the alpha(CS) mutation (al pha(CS)alpha) is only one-half of that by the alpha 2 alpha 1-globin g ene of a chromosome with a 3.7 or 4.2 kb deletion, explaining the grea ter severity of, and higher Hb H level in Hb H patients with the alpha (CS)alpha condition (alpha(CS)alpha/--) as compared to those with the three gene deletion (-alpha/--). The methodology could be useful as a preliminary screening for the presence of point mutations leading to t he functional loss of a single alpha-globin gene, provided common dele tional alleles have been excluded.