HEMOGLOBIN DHOFAR IS LINKED TO THE CODON-29 C-]T (IVS-1 NT-3) SPLICE MUTATION WHICH CAUSES BETA(+) THALASSEMIA

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 beta-globin chain (beta 58 Pro --> Arg) and is therefore not consistent with the observed prop ortion of Hb Dhofar, as in both this and the original case, it constit uted only 15% of the total haemoglobin. We have determined the basis o f the low expression of this mutant, which is due to its linkage to a thalassaemic splicing mutation on the same beta-globin gene at codon 2 9 (C --> T). The finding of this thalassaemia mutation linked to Hb Dh ofar not only explains the low level of Hb Dhofar, but also provides e vidence that the codon 29 C --> T, IVS-1 splice junction mutation caus es a beta(+) form of thalassaemia.