BETA-THALASSEMIA IN GERMANY - MOLECULAR-G ENETICS AND CLINICAL PHENOTYPE IN THE IMMIGRANT AND IN THE NON-IMMIGRANT POPULATIONS

Background In Germany there are about 300-400 patients with homozygous beta-thalassaemia who immigrated from endemic regions mostly in the M editerranean. In the non-immigrant population beta-thalassaemia is rar e with only single case reports of homozygous patients. Heterozygous b eta-thalassaemia, however, is more common and must be considered in th e differential diagnosis of hypochromic anemia. Patients and Methods H ere, clinical and molecular data of 221 homozygous patients from immig rant families and 256 non-immigrant German heterozygous individuals ar e presented. Results Clinically, 87% (n=192) of the homozygotes are re gularly transfused and classified as thalassaemia major (TM). The othe r 13% (n=29) are not (regularly) transfused and thus classified as tha lassaemia intermedia (TI). There is a wide spectrum 39 beta-globin gen e mutations and even the most common three, IVSI-110 G-A, NS 39, and I VSI-6 T-C occur with relatively low frequencies of 28%, 22%, and 9%, r espectively. In 17/29 (58%) TI patients,, mild'' mutations are found t hat inactivate the affected gene incompletely. In 16/29 (55%) there ar e mutations that are associated with increased gamma-globin gene activ ity. alpha-Thalassaemia is rare and only found in 3/29 TI-patients. In the 256 Germans with heterozygous beta-thalassaemia there are 27 diff erent beta-globin gene mutations. The 3 most common are Mediterranean mutations together accounting for 61%. Also relatively common (5%; n=1 3) is an otherwise rare frameshift mutation of codon 83 (FS83 Delta G) . The other mutations occur in <10 individuals only. Two mutations des cribed 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 s ingle G in codon 15/16 (FS 15/16 Delta G). Conclusions Taken together, a plausible molecular pathogenesis for the observed phenotype (TM vs. TI) can be identified in most homozygous patients thus allowing for r ational counselling of the affected families. In heterozygous Germans beta-thalassaemia has probably been imported from the Mediterranean in about 2/3 of the cases whereas in the remaining 1/3 it has probably o riginated locally.