Thalassemias and Other Hemoglobinopathies in Former Yugoslavia

This review summarizes our results on the epidemiology and molecular basis of thalassemias and other hemoglobinopathies in the republics and provinces of the Former Yugoslavia. Over the past 40 years, surveys of more than 37,000 school children and more than 1,600 adults, from all over Former Yugoslavia, except Slovenia, have shown an average incidence of β-thalassemia (β-thal) trait of 1.2%, ranging from 2.9% in the south (Macedonia) to 0.8% in the northwest (Croatia). The frequency of δβ-thal was 0.2%, while that of Swiss type hereditary persistence of fetal hemoglobin (HPFH) was 0.4%. Screening of 12,680 newborns has shown that the frequency of α-thal trait was 1.5%. The molecular basis of the thalassemias in the populations of Former Yugoslavia has been completely defined. More than 700 β-thal chromosomes have been studied and their molecular defect was determined. In the Macedonian population, 16 different β-thal mutations were detected, four of which (IVS-I-110, G→A; IVS-I-6, T>C; IVS-I-1, G>A and codon 39, C>T) accounted for 85% of all β-thal chromosomes. In the Croatian population, 18 different β-thal alleles were detected. Four new mutations [nucleotide (nt) -87, C>A; IVS-II-850, G>C; initiation codon mutation T>C; polyadenylation signal (poly A), AATAAA>AATGAA)] and one new deletion (1605 bp), were characterized. Molecular analyses of DNA from over 50 unrelated cases with δβ-thal have shown that this condition was mainly caused by a 13 kb deletion (Sicilian type); in one family, a deletion of >18 to 23 kb (Macedonian-Turkish type), and in another, a deletion of 148 kb (Yugoslavian type of εγδβ-thal) of the β-globin gene complex, were discovered. Molecular analyses of α-thal from Former Yugoslavia revealed the following defects: the -20.5, -17.5 and -3.7 kb deletions, a 5 nt deletion, and Hb Icaria [α142, Term→Lys (TAA>TCA in α2)]. The incidence of abnormal hemoglobins (Hbs) in Former Yugoslavia was 0.3%. Five different α chain variants in 16 families, 16 different β chain variants in 61 families, one δ chain variant in one family, two types of Hb Lepore in 122 families and two γ chain variants, have been characterized.