Special Feature Hemoglobinopathies in Yugoslavia: an Update

Abstract

This paper summarizes information on the epidemiology and molecular basis of hemoglobinopathies in Yugoslavia. Over the past 25 years, population surveys of more than 28,000 school children from all over the country, except Slovenia, have shown that the average incidence of β-thalassemia (β-thal) trait is 1.2%, ranging from 2.9% in the south (Macedonia) to 0.8% in the northwest (Croatia). The frequency of δβ-thal is 0.2%, while the frequency of the Swiss type of hereditary persistence of fetal hemoglobin (HPFH) is 0.4%. Screening of 6,400 newborns has shown that the frequency of α-thal trait is 1.6%. The molecular basis of the different forms of β-thal among Yugoslavians has been almost completely defined. Over 250 β-thal chromosomes have been studied, and in over 90% the molecular defect was determined. Eighteen different β-thal mutations have been detected, three of which (IVS-1-110, G→A; IVS-1-6, T→C; IVS-1-1, G→A) account for more than 70% of all β-thal chromosomes. Four new mutations [-87 (C→A); IVS-II-850 (G→C); initiation codon mutation T→C; poly A (AATAAA→ AATGAA)] and one new deletion (1605 bp) have been characterized. Molecular analyses of DNA from over 30 unrelated cases with δβ-thal have shown that this condition is mainly caused by a 13 kb deletion (Sicilian type); in one family a deletion of >18 to 23 kb (Macedonian type), and in another family a deletion of 148 kb (Yugoslavian type of γδβ-thal) of the globin gene complex was discovered. Limited studies of α-thal in Yugoslavia have shown the following types of molecular defects: ~20.5 kb deletion, ~17.5 kb deletion, -3.7 kb deletion, 5 nucleotide (nt) deletion, and Hb Icaria. The incidence of abnormal hemoglobins (Hbs) in Yugoslavia is 0.3%. Five different α chain variants among 21 families, 15 different β chain variants among 53 families, one δ chain variant in one family, one variant with a deleted residue in one family, and two types of Hb Lepore among 122 families, have been observed.