Developmental Effect of the XmnI Site on G -Globin Gene Expression Among Newborn Hb F-Malta-I [G 117(G19)His→Arg, CAT→CGT] Heterozygotes and Adult +-Thalassemia Homozygotes

• Published in: Hemoglobin 2007, Vol.31 (1), p.71-82
• Main Authors: Pulis, Svetlana, Scerri, Christian A., Schembri Wismayer, Pierre, Galdies, Ruth, Bezzina Wettinger, Stephanie, Felice, Alex E.
• Format: Article
• Language: English
• ISSN: 0363-0269; 1532-432X
• DOI: 10.1080/03630260601057187

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′ 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.