Comparative in vivo expression of beta(+)-thalassemia alleles

Double heterozygotes who inherit one abnormal though stable P-globin varian t in association with a molecularly identified beta(+)-thalassaemia allele provide unique opportunities to quantify the in vivo expression of particul ar beta(+)-thalassemia alleles. The globin products of the two alleles can be separated, quantified and the output of the beta(+)-thalassaemia allele expressed as the MCH-PA in pg beta(A)-globin/beta(+)-thalassemia allele/RBC = 0.5 MCH xHb A%, In this communication we provide new quantitative data o n the expression of five mutations as follows: the beta(+)-87 (C-->G) = 3.8 pg beta(4)-globin/beta(+)-thalassemia allele/RBC (n = 1); the beta(+) IVs- I-1 (G-->A) = 0.2 pg beta(A)-globin/beta(+)-thalassemia allele/RBC (n = 1); the beta(+) IVS-I-6 (T-->C)= 2.9 pg beta(A)-globin/beta(+)-thalassemia all ele/RBC (n = 7); the beta(+) IVS-I-110 (G-->A)= 1.1 pg beta(A)-globin/beta( +)- thalassemia allele/RBC (n = 13), and the beta(+) IVS-II-745 (C-->G) = 1 .74 pg beta(A)-globin/beta(+)-thalassemia allele/RBC (n = 2). The values ob tained are compared with those of other beta(+)-thalassemia alleles from th e literature It can be seen that the MCH-beta(A) value may be a correct ind ex of thalassemia severity useful for the correlation of genotype with phen otype, and for understanding the effects of mutations in beta-globin genes on pathophysiologically meaningful beta-globin gene expression.