Hb Chad or α₂23(B4)GLU→LYSβ₂ Observed in Members of a Surinam Family in Association with α-Thalassemia-2 and with HB S

Abstract

Three different hemoglobinopathies, i.e. Hb S, Hb Chad [α23 (B4)Glu→Lys], and α-thalassemia-2 (−3.7) have been observed in eight members of a family from Surinam. The proposita had all three abnormalities, while her mother and four of her half-brothers had Hb Chad together with an α-thalassemia-2 heterozygosity or homozygosity. Gene mapping and dot-blot analysis of amplified DNA identified a G→A mutation in codon 23 of the α2αl hybrid gene resulting in the Glu→Lys substitution. The quantity of the α-Chad chain averaged 31.5% in its carriers with an additional α-thalassemia-2 heterozygosity [-α^Cnad(−3.7 kb)/ α α], and 43% in the two carriers with an additional α-thalassemia-2 homozygosity [-α^Chad(−3.7 kb)/- α (3.7 kb)]. These quantities are considerably higher than those reported for families from Chad, China, and Japan; the low levels of 14.5-24% Hb Chad in members of previously reported cases suggest a mutation on a chromosome with two α-globin genes [α α^Chad/α α or α^Chadα/ α α].