The greekaγβ+‐hpfh observed in a large black family

Abstract
Several members of a Black family with a heterozygosity for an AγGβ+‐HPFH, shown in 1969 to have relatively low levels of Hb F and a low glycine to alanine ratio in the γ chain of this Hb F, were reinvestigated. Thirteen of 30 available family members in two generations had the heterozygous form of this condition, which was characterized by a decreased level of Hb A2, an average Hb FAD value of 13.3%, an equal distribution of Hb F over the red cells, and normal hematological values. The γ chain composition of isolated Hb F was determined by reversed phase high performance liquid chromatography for all 13 heterozygotes and showed an average Aγ value of 84.5 %. Hybridization with synthetic oligonucleotides, specific for normal and mutant sequences at positions 111–129 5′ to the Aγ globin gene, identified a G ± A base substitution at position 117, similar to that seen in subjects with the Greek Aγ‐HPFH. Our data support conclusions by others [15,16,30] that this replacement is causative of the increased Aγ chain synthesis in this condition. Haplotype analysis supported the suggestion that the G ± A substitution occurred as an independent event in this Black family.