Comparative in vivo expression of β⁺-thalassemia alleles

Double heterozygotes who inherit one abnormal though stable β-globin variant in association with a molecularly identified β+-thalassaemia allele provide unique opportunities to quantify the in vivo expression of particular β+-thalassemia alleles. The globin products of the two alleles can be separated, quantified and the output of the β+-thalassaemia allele expressed as the MCH-β(A) in pg β(A)-globin/β+-thalassemia allele/RBC = 0.5 MCH x Hb A%. In this communication we provide new quantitative data on the expression of five mutations as follows: the β+-87 (C→G) = 3.8 pg β(A)-globin/β+-thalassemia allele/RBC (n = 1); the β+ IVS-I-1 (G→A) = 0.2 pg β(A)-globin/β+-thalassemia allele/RBC (n = 1); the β+ IVS-I-6 (T→C) = 2.9 pg β(A)-globin/β+-thalassemia allele/RBC (n = 7); the β+ IVS-I-110 (G→A) = 1.1 pg β(A)-globin/β+-thalassemia allele/RBC (n = 13), and the β+ IVS-II-745 (C→G) = 1.74 pg β(A)-globin/β+-thalassemia allele/RBC (n = 2). The values obtained are compared with those of other β+-thalassemia alleles from the literature. It can be seen that the MCH- β(A) value may be a correct index of thalassemia severity useful for the correlation of genotype with phenotype, and for understanding the effects of mutations in β-globin genes on pathophysiologically meaningful β-globin gene expression.