HETEROZYGOUS BETA-THALASSEMIA WITH THALASSEMIA-INTERMEDIA PHENOTYPE

In this study we investigated the molecular bases of the beta-thalasse mia intermedia phenotype in six patients belonging to two unrelated fa milies of Sardinian descent. Sequence analysis of the beta globin gene from these patients detected, as the sole abnormality, the heterozygo sity for the codon 39 nonsense mutation, The A gamma and G gamma promo ters as well as the HS2 and HS3 core sequences of the beta globin LCR from these patients, did not show any non-polymorphic nucleotide varia tion from the consensus sequence. One of the parents was heterozygous for codon 39 nonsense mutation but showed the beta-thalassemia carrier phenotype; the other was hematologically normal and had an entirely n ormal beta globin gene sequence. In both families, other members showe d the typical hematological phenotype, clinically silent, of heterozyg ous beta thalassemia, To explain the thalassemia intermedia phenotype, we postulated the presence of an unknown molecular defect interacting with the beta globin gene mutation. Haplotype analysis excluded that this postulated defect lies in the beta globin gene cluster. (C) 1998 Wiley-Liss, Inc.