Molecular characterization of a normal Hb A2 beta-thalassaemia determinant in a Sardinian family

In this study we have carried out haplotype analysis at the beta-globin gene cluster and defined the beta-thalassaemia mutations in a large Sardinian family, ascertained through a proband with thalassaemia major, in which several members were carriers of a beta-thalassaemia allele characterized by microcytosis, hypochromia and normal Hb A2 levels (type 2 normal Hb A2 heterozygous beta-thalassemia). The proband was a compound heterozygote for the beta zero 39 and the beta + IVS-2, nt 745 mutations and all the beta-thalassaemia heterozygotes with normal Hb A2 showed the beta + IVS-2, nt 745 mutation, always associated with haplotype VII. Because of the consistent association of a specific beta-thalassaemia mutation and normal Hb A2 levels, we postulate that this beta-thalassaemia chromosome carries a delta gene (delta-thalassaemia) which is unable to increase the delta-globin output in response to beta-thalassaemia.