Alpha globin gene duplications in beta thalassemia patients with intact beta globin gene.

In this paper we report the study carried out in five out of eleven families previously described, using MPLA assay of the alpha globin genes (SALSA MLPA Kit, HBA, MRC-Holland, the Netherlands). In two families belonging to the silent β-thalassemia-like phenotype, we detected two different duplications of the complete α-globin gene cluster including the upstream regulatory element HS-40, of approximately 70 and 130 kb respectively. The growing improvement and optimization of molecular biology technologies, led us to characterize, at molecular level, several undefined patients with an atypical thalassemic phenotype, whose studies begun in our laboratory more than 20 years ago. The results described here are very exciting for the comprehension of the molecular pathology of β-thalassemia and have implications for prognosis and prevention of the disease. The presence of αduplication should be considered in patients heterozygotes for βthalassemia with low/normal MCV, normal HbA2 levels and markedly unbalanced globin-chain synthesis.