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

Abstract

Among several hundred apparently healthy Yugoslavian adults with slightly elevated levels of fetal haemoglobin, we have identified two distinct abnormalities. (a) A G gamma A gamma(delta beta)0-thalassaemia heterozygosity with an approximately 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; Carè 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.(+)G gamma.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----T mutation at position--158 5' to the G gamma chain [(+)G gamma], identified through analyses of Xmn I digests, was present at both G gamma globin genes. This mutation is known to be associated with increased G gamma chain production (Gilman & Huisman, 1985), and thus is responsible for the increased G gamma chain production in these heterozygotes. The condition is different from the (+)G gamma.(+)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.

An Indonesian Family with the Southeast Asian Type of α-Thalassemia-1 and a γ-Globin Gene Triplication

“…All adults with a y-globin gene triplication are hematologically normal, al though variability in the increase in Hb F production and in the level of Gy chains in this Hb F has been re ported [20]. The anomaly present in our propositus closely resembles that seen in a few families from Yu goslavia [19]. The Yugoslavian heterozygotes are healthy adults with slightly elevated levels of Hb F (the average value of 5.6% is definitely higher than that seen in our propositus and her two daughters), high Gy values (>90%) and comparable gene map ping data (i.e.…”

“…In the DNA di gests of most such cases, a larger Xmn I fragment is seen, namely 13 kb if the Xmn I site is absent or 12 kb if it is present. However, occasionally two Xmn I fragments are found which hybridize to the yIVS-II probe, one 7 kb and a second 5 kb [19]; these were also observed for our propositus ( fig. 2, bottom).…”

“…2, bottom). Such data indicate that the C -T substitution, and thus the Xmn I restriction site, is present at -158 for both the 5' and the middle y-globin genes of the triplication [19], The two children (III-l and 111-2) inherited this triplication from their mother and a normal chromo some without the C-*T substitution at -158 from the father; as a result, three fragments (8 kb from the nor mal chromosome and 7 and 5 kb from the triplicated chromosome) have been found (fig. 2, bottom).…”

Molecular Characterization of Italian Chromosomes Carrying the Lepore Boston Gene

“…The Bam HI site 3' to the deletion, present in the majority of the cases, was reported to be absent in 2 Yugoslavian carriers [24].…”

A Short Review of Human γ-Globin Gene Anomalies

“…(5) A y-globin gene triplication is the expected counterpart of the y-globin gene deletion, and also re sults from a crossover between mismatched chromo somes [8,15,17]. Thus, three y-globin genes are lo cated on one chromosome (yyy).…”