GγAγ(δβ)°‐thalassaemia and a new form of γ globin gene triplication identified in the Yugoslavian population

Abstract

Among several hundred apprently healthy Yugoslavian adults with slightly elevated levels of fetal haemoglobin, we have identified two distinct abnormalities. (a) A G.gamma.A.gamma.(.delta..beta.).degree.-thalassaemia heterozygosity with an .apprx. 15 kb deletion which involves part of the .delta. globin gene and the .beta. globin gene. This deletion is probably the same as that seen among Italians (Ottolenghi et al, 1982; Care et al, 1984). (b) A nondeletion form of hereditary persistence of Hb F which is caused by a .gamma. globin gene triplication of the (+)G.gamma..cntdot.(+)G.gamma..cntdot.A.gamma. type. It is characterized by the presence of some 5% Hb F in the heterozygote containing nearly 100% G.gamma. chains. The C .fwdarw. T mutation at position -158 5'' to the G.gamma. chain [(+)G.gamma.], identified through analyses of Xmm I digests, was present at both G.gamma. globin genes. This mutation is known to be associated with increased G.gamma. chain production (Gilman and Huisman, 1985), and thus is responsible for the increased G.gamma. chain production in these heterozygotes. The condition is different from the (+)G.gamma..cntdot.(+)G.gamma. nondeletion type of HPFH which has been observed in heterozygotes of two Black families, and is associated with the presence of 3-4% Hb F (with mainly G.gamma. chains) in heterozygotes.