Identification and molecular characterization of the --CAMPANIA deletion, a novel alpha zero-thalassemic defect, in two unrelated Italian families

We describe a novel deletion form of alpha-thalassemia which removes a region of 31 kilobase encompassing the entire a-globin gene cluster. In association with the - alpha+ 3.7 deletion this defect gave rise to a typical hemoglobin H (HbH) disease in two unrelated boys of Southern Italian descent. The molecular characterization of the deletion revealed involvement of Alu repeat sequences, indicating that this rearrangement was originated from an event of unequal recombination. Furthermore, sequence analysis of the junctional region and genotyping of polymorphic sites flanking the 5’ and 3’ breakpoints suggest a unique origin for this mutation in these two patients. Our study contributes to define the wide spectrum of mutations that underlie the thalassemia syndromes in the Mediterranean area and provides support to prevention programs of a-thalassemia based on molecular screening and prenatal diagnosis in couples at risk.