Segmental duplications involving the α-globin gene cluster are causing β-thalassemia intermedia phenotypes in β-thalassemia heterozygous patients

We describe two cases of simple heterozygosity for the common β°-thalassemia mutation β39 (C → T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or red cell enzyme deficiencies were excluded. In one case a triplication of the α-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the α-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the α-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-α^3.7 triplication in trans, resulting in a total of 7 active α-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active α-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of α-globin genes duplication defects in cases of β-thalassemia heterozygotes with thalassemia intermedia phenotypes.