Molecular characterization of a normal Hb A2β‐thalassaemia determinant in a Sardinian family

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Abstract
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..degree.-39 and the .beta.+ IVS-2, nt 745 mutations and 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.