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Hemoglobinopathies in Yugoslavia: an update.

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 beta-thalassemia (beta-thal) trait is 1.2%, ranging from 2.9% in the south (Macedonia) to 0.8% in the northwest (Croatia). The frequency of delta beta-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 alpha-thal trait is 1.6%. The molecular basis of the different forms of beta-thal among Yugoslavians has been almost completely defined. Over 250 beta-thal chromosomes have been studied, and in over 90% the molecular defect was determined. Eighteen different beta-thal mutations have been detected, three of which (IVS-I-110, G-->A; IVS-I-6, T-->C; IVS-I-1, G-->A) account for more than 70% of all beta-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 delta beta-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 epsilon gamma delta beta-thal) of the globin gene complex was discovered. Limited studies of alpha-thal in Yugoslavia have shown the following types of molecular defects: approximately 20.5 kb deletion, approximately 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 alpha chain variants among 21 families, 15 different beta chain variants among 53 families, one delta 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.