Molecular analysis of the Turkish form of deletion‐inversion (δβ)° thalassaemia

Two unrelated (δβ)°‐thalassaemia patients from Southern Turkey are presented. DNA studies indicated that both of them are homozygous for the Turkish type of (δβ)°‐thalassaemia characterized by one large deletion of 11.5 kb including the δ and β 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 β‐globin gene cluster of deletion‐inversion type of (δβ)°‐thalassaemia, IVS‐I‐6 and β‐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 δ, Gγ and Aγ 5′ flanking regions and the second intervening sequence (IVS‐II) of Aγ and Gγ genes indicated the presence of close similarities between the chromosome carrying the Turkish form of deletion‐inversion δβ)°‐thalassaemia and the chromosome associated with β‐39 nonsense mutation in haplotype II. These two chromosomes are characterized by the presence of a 4 base pair deletion in the AγT globin gene promoter. A C → T alteration at position −199 5′ to the δ gene was also found to be associated with the Turkish type of (δβ)°‐thalassaemia and β‐39 chromosome.