Developmental Effect of the XmnI Site on ^Gγ-Globin Gene Expression Among Newborn Hb F-Malta-I [^Gγ117(G19)His→Arg, CAT→CGT] Heterozygotes and Adult β⁺-Thalassemia Homozygotes

Abstract

Hb F-Malta-I [^Gγ117(19)His→Arg, CAT→CGT] is a stable and benign variant of Hb F found in 1.8% of Maltese newborn. We studied 120 Hb F-Malta-I heterozygotes and four Hb F‐Malta-I homozygotes. The mean proportion of ^Gγ-F-Malta-I in Hb F was 0.26 ± 0.03 for the Hb F-Malta-I heterozygotes and 0.58 ± 0.06 for the Hb F-Malta-I homozygotes. The Hb F-Malta-I allele was shown to occur on a background of the common Mediterranean haplotype Va [+ + − − − − − + + −]. Furthermore, the common Mediterranean haplotypes Va, IIIb [− + + + − + + + + −], I [+ + − − − − − + + +] and II [− + − + + − + + + +] accounted for most (66.2%) of the wild-type alleles among the tested Hb F-Malta-I heterozygotes.

Different genotypes at the 5′ ϵ HincII, ^Gγ and ^Aγ HindIII, and 3′ψβ HincII sites (but not at the 5′ ^Gγ XmnI site) were found to be linked to significant variations in the proportion of ^Gγ-F-Malta-I and ^Gγ-globins in the Hb F of newborn Hb F-Malta-I heterozygotes. Moreover, the 5′ ^Gγ XmnI site was found to be associated with variations in Hb F and ^Gγ-globin levels in a population of adult Maltese β-thalassemia (thal) homozygotes. This implies that a determinant linked to the XmnI site which effects ^Gγ-globin gene expression is active in anemic adults but not in normal infants.

Keywords:

• γ-Globin
• Hb F-Malta-I
• Fetal hemoglobin (Hb)
• Haplotypes