Hemoglobin Abnormalities in a Black Family with Hb S, Hereditary Persistence of HB F, and A γ Chain Variant; a Reevaluation Through Gene Mapping

Abstract

Members of a Black family from Georgia who were investigated for the first time in 1960 (Ref. 2) and several times thereafter (Refs. 8,19,20) were reinvesti-gated through DNA restriction endonuclease analyses and haplotyping, while the γ chain heterogeneity of the Hb F was reevaluated using a newly developed HPLC procedure. Four different abnormalities were present, (a) Heterozygosity for ^Gγ^Aγ⁻HPFH type II characterized by a large deletion involving the δ and β globin genes with a 5′ end within the ψβ gene. (b) Heterozygosity for an -ϵ-^Gγ-^Gγ-ψβ-δ-β^S-chromosome, thus carrying a β^S globin gene and two ^Gγ genes instead of one ^Gγ and one ^Aγgene. (c) Heterozygosity for an -ϵ-^Gγ-^Aγ-^T-ψβ-δ-β^S-chromosome, carrying the β^S globin gene and an allele of the ^aγ (or ^aγ^I) gene. These three chromosomes occurred in combination with each other, resulting in SS and S-HPFH conditions, and with a normal -ϵ-^Gβ-^Aβ-ψβ-δ-β^A-chromosome resulting in the HPFH and Hb S het-erozygosities. The presence of the -^Gγ-^Gγ- and -^Gγ-^Aγ^T-chromosomes in the one SS patient was resonsible for the high ^Gγ value (average 75%), 25% ^aγ^T chain, and for the absence of the ^Aγ^I chain. (d) An α-thalasse-mia-2 heterozygosity in one member.