A Family With Segregating Triplicated Alpha Globin Loci and Beta Thalassemia

In this article we report a Sardinian family, in which a β-thalassemia gene and a triple α-globin loci, counterpart of the rightward deletion type α-thalassemia-2, were segregating. The analysis of the genotype-phenotype correlations in the different family members allowed us to give an outline of the manifestations associated with different genotype combinations. The heterozygote for the triple α-loci showed no consistent abnormal clinical or hematologic characteristics and presented balanced α/β-globin chain synthesis. In the homozygous state for this lesion, the only phenotypic expression was a slightly imbalanced globin chain synthesis. The combination of heterozygous β-thalassemia with the heterozygous state for the triple α-globin loci produced no clinical manifestations and showed a hematologic phenotype indistinguishable from that of heterozygous β-thalassemia. On the other hand, the combination of the homozygous state for the triple α-globin gene loci and the heterozygous state for β-thalassemia produced a clinical picture of thalassemia intermedia with a very mild clinical course, minor increase of fetal hemoglobin (HbF) levels, and a pronounced imbalance of globin chain synthesis.