Globin gene mapping studies in Sardinian patients homozygous for beta zero Thalassaemia

The genetic factors responsible for the relatively mild clinical phenotypes of some cases of homozygous beta zero thalassaemia (thalassaemia intermedia) in Sardinia have been evaluated. The frequency of deletion forms of alpha thalassaemia was higher in patients with thalassaemia intermedia (6/8) than in those with thalassaemia major (6/17). The beta globin gene clusters were also studied, first to determine whether there were any rearrangements of the gamma genes, and second to see whether the restriction fragment length polymorphism patterns (haplotypes) of the two groups of patients were similar. The structure of the gamma genes was normal in all the patients with the single exception of a thalassaemia major patient with a triplicated gamma gene arrangement. The beta globin gene cluster haplotypes of the two groups of patients were not significantly different. However, the frequency of the various haplotypes in the thalassaemic as compared to the normal (beta A) chromosomes was different. This finding is of potential value in the antenatal diagnosis of homozygous beta thalassaemia in this population.