Molecular analysis of the Turkish form of deletion-inversion (delta beta)(0) thalassaemia

Two unrelated (delta beta)(0)-thalassaemia patients from Southern Turkey are presented. DNA studies indicated that both of them are homozygous for the Turkish type of (delta beta)(0)-thalassaemia characterized by one large deletion of 11.5 kb including the delta and beta globin genes at the 5' end and one small deletion of 1.6 kb at the 3' end, which are separated by an inverted 7.6 kb long DNA segment that includes L1 repetitive sequence. In the present study a PCR-based method was performed to produce a unique deletion-specific product and subjected to sequence analysis for the determination of the breakpoint. DNA polymorphisms in the beta-globin gene cluster of deletion-inversion type of (delta beta)(0)-thalassaemia, IVS-I-6 and beta-39 globin genes were examined. Analysis of sequence variations in regulatory regions including the 5' hypersensitive site-2 of the locus control region (LCR), the delta, (G)gamma and (A)gamma 5' flanking regions and the second intervening sequence (IVS-II) of (A)gamma and (G)gamma genes indicated the presence of close similarities between the chromosome carrying the Turkish form of deletion-inversion (delta beta)(0)-thalassaemia and the chromosome associated with beta-39 nonsense mutation in haplotype II. These two chromosomes are characterized by the presence of a 4 base pair deletion in the (A)gamma(T) globin gene promoter. A C --> T alteration at position -199 5' to the delta gene was also found to be associated with the Turkish type of (delta beta)(0)-thalassaemia and beta-39 chromosome.