An AγType of Nondeletional Hereditary Persistence of Fetal Hemoglobin With a T→ C Mutation at Position -175 to the Cap Site of the AγGlobin Gene

The nondeletional types of hereditary persistence of fetal hemoglobin (ndHPFH) concern the continued synthesis of hemoglobin (Hb) F with either Gγor Aγchains in amounts varying from 5% to 30%. Several mutations have been identified in either the Aγor Gγpromoter which are considered causative to the continued production of one of the two 7 chains because the substitutions occur in sequence motifs essential for the expression characteristics of the γ-globin gene in the 3’ position. We report the discovery of a T → C mutation at position - 175 in the Aγpromoter which was associated with a greatly increased level of Hb F (with mainly Aγ) and a decreased level of Hb A in the one (Black) heterozygote who had a βcgene in trans. The same mutation has been observed in the Gγpromoter of a Black heterozygote who had high levels of Hb F with Gγchains 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 Gγpromoter. © 1989 by Grune & Stratton, Inc.