Homozygous βd`-39 Mutation with Thalassemia Intermedia in Northern Sardinia: Clinical, Hematological and Molecular Analysis

Abstract

In this study, we investigated the clinical and hematological features and carried out α- and β-globin gene analyses in 11 Sardinian adult βd`-thalassemia homozygotes from Northern Sardinia who were not transfusion-dependent. Oligonucleotide analysis revealed in nine out of 11 patients the nonsense mutation at codon 39, which was associated either with haplotype II or IX (14/16 and 2/16 chromosomes, respectively). Haplotype II was linked to the A<sub>γ</sub>T mutation. The G<sub>γ</sub> globin level ranged from 50 to 70%. Four out of nine patients (44%) were heterozygous and 3/9 (33%) homozygous for the rightward deletional type of α-thalassemia; two (22%) had the normal α-gene complement. Patients who were α-thalassemia homozygotes (-α/-α) showed a more balanced globin chain synthesis ratio. This study confirms that α-thalassemia may ameliorate the clinical picture of homozygous βd`-thalassemia.