An (A)? type of nondeletional hereditary persistence of fetal hemoglobin with a T ? C mutation at position -175 to the cap site of the (A)? globin gene

The nondeletional types of hereditary persistence of fetal hemoglobin (ndHPFH) concern the continued synthesis of hemoglobin (Hb) F with either (G)? or (A)? chains in amounts varying from 5% to 30%. Several mutations have been identified in either the (A)? or (G)? promoter which are considered causative to the continued production of one of the two ? chains because the substitutions occur in sequence motifs essential for the expression characteristics of the ?-globin gene in the 3' position. We report the discovery of a T ? C mutation at position -175 in the (A)? promoter which was associated with a greatly increased level of Hb F (with mainly (A)?) and a decreased level of Hb A in the one (Black) heterozygote who had a ß(c) gene in trans. The same mutation has been observed in the (G)? promoter of a Black heterozygote who had high levels of Hb F with (G)? chains only. A detailed comparison between these two individuals indicated significant differences in the levels of Hb F and Hb A which may result from an additional mutation at position -158 in the (G)? promoter.