Haemoglobin Dhofar is linked to the codon 29 C –→ T (IVS-1 nt – 3) splice mutation which causes /3+ thalassaemia

Investigations of a young man with apparent thalassaemia minor showed that he was a heterozygote for a rare abnormal haemoglobin variant, Hb Dhofar. The amino acid replacement is in the /3-globin chain (j358 Pro – Arg) and is therefore not consistent with the observed proportion of Hb Dhofar, as in both this and the original case, it constituted only 15% of the total haemoglobin. We have determined the basis of the low expression of this mutant, which is due to its linkage to a thalassaemic splicing mutation on the same /3-globin gene at codon 29 (C –> T). The finding of this thalassaemia mutation linked to Hb Dhofar not only explains the low level of Hb Dhofar, but also provides evidence that the codon 29 C –> T, IVS-1 splice junction mutation causes a (3 ⁺ form of thalassaemia.