Fetal hemoglobin expression in compound heterozygotes for -117 (G→A) ^Aγ HPFH and β⁰39 nonsense thalassemia

Abstract

The-117(G→A) Aγ hereditary persistence of fetal hemoglobin (Greek HPFH) and β039-thal mutations are rather frequent in Sardinia so that their interaction is to be expected. Characterization of eight compound heterozygotes for these defects indicated that HPFH was linked to haplotype VII and β039-thal to haplotype II. Haplotype II β039-thal chromosome carries the AγT gene which is a useful marker of γ-gene expression. Since the Hb F level in these compound heterozygotes was significantly higher than in 46 -117 HPFH carriers, the Aγt, and Gγ globin level was determined. AγT was underexpressed while Gγ was significantly increased, which suggests that in -117 Aγ HPFH/β039-thal healthy subjects the increase in Hb F production is determined only by the -117 mutated Aγ gene and the adjacent Gγ gene