A Further Case of ^Gγ-β⁺ Hereditary Persistence of HB F Associated to the -202 CG Mutation in the ^Gγ Promoter Region

Abstract

The condition known as the hereditary persistence of fetal hemoglobin (HPFH) is a heterogeneous group of genetically determined anomalies characterized by the presence of increased amounts of Hb F in adult life in the absence of erythropoietic stress (1). Restriction endonuclease analysis has demonstrated that many of these syndromes are due to large deletions in the non-α globin cluster (reviewed in Refs. 1 and 2), whereas in other cases gene sequencing has been necessary to uncover single base substitutions. Point mutations in the promoter regions of the ^Gγ and ^Aγ genes have described (3, 4, 5, 6), leading to the suggestion that a single base change can result in persistent gene expression. However, the possibility of simple plymorphisms in linkage disequilibrium cannot be excluded. In particular a CG base change at position -202 of the ^Gγ gene has been found in 14 cases (six unrelated chromosomes) to be associated with Hb F levels in the rage 13.3-38.1%, most of it being of the ^Gγ type (6, 7, 8). We report here another family of African ancestry with the same base substitution. It was found in a heterozygote for Hb S, in whom we also determined the haplotype at 11 polymorthic restriction sites.