Beta-thalassaemia in the immigrant and non-immigrant German populations

In Germany homozygous beta-thalassaemia mainly occurs in the immigrant population from endemic regions. In non-immigrants beta-thalassaemia is rare. Heterozygous beta-thalassaemia minor, however, is more common and must be considered in the differential diagnosis of hypochromic anaemia. The clinical and molecular data of 221 homozygous patients and 256 non-immigrant German heterozygous individuals are presented. Clinically, 87% (n = 192) of the homozygotes are classified as thalassaemia major (TM) and the other 13% as thalassaemia intermedia (TI). There is a wide spectrum of 39 thalassaemia mutations which occur with relatively low frequencies in individual cases. In 17/29 TI patients 'mild' mutations have been found and in 16/29 there are mutations that are associated with increased gamma-globin gene activity. alpha-Thalassaemia is rare and found only in 3/29. In the 256 Germans with heterozygous beta-thalassaemia there are 27 different thalassaemia mutations. The three most common are Mediterranean, together accounting for 61%. Also relatively common (5%) is an otherwise rare frameshift mutation of codon 83 (FS83 deltaG). The other mutations occur in < 10 individuals. Two mutations described here are novel. One of them affects position -2 of the intron 1 splice acceptor site (IVSI-129 A-G) and the other is a deletion of a single G in codon 15/16 (FS 15/16 deltaG). These data suggest that beta-thalassaemia in Germans was introduced from the Mediterranean in about two-thirds of cases and that the remaining third has probably originated locally.