| Abstract: | In this study we investigated the molecular bases of the β-thalassemia intermedia phenotype in six patients belonging to two unrelated families of Sardinian descent. Sequence analysis of the β globin gene from these patients detected, as the sole abnormality, the heterozygosity for the codon 39 nonsense mutation. The Aγ and Gγ promoters as well as the HS2 and HS3 core sequences of the β globin LCR from these patients, did not show any non-polymorphic nucleotide variation from the consensus sequence. One of the parents was heterozygous for codon 39 nonsense mutation but showed the β-thalassemia carrier phenotype; the other was hematologically normal and had an entirely normal β globin gene sequence. In both families, other members showed the typical hematological phenotype, clinically silent, of heterozygous β thalassemia. To explain the thalassemia intermedia phenotype, we postulated the presence of an unknown molecular defect interacting with the β globin gene mutation. Haplotype analysis excluded that this postulated defect lies in the β globin gene cluster. Am. J. Hematol. 57:43–47, 1998. © 1998 Wiley-Liss, Inc. |
