South-Italy beta°-thalassemia: a novel deletion not removing the gamma-globin silencing element and with 3' breakpoint in a hsRTVL-H element, associated with beta°-thalassemia and high levels of HbF.

The levels of fetal hemoglobin (HbF) are the major modifier of disease severity in patients with beta-thalassemia. Here is reported a patient with completely absent beta chains that at diagnosis was almost asymptomatic because high levels of HbF (10 g/dl). The patient was a genetic compound for the beta°-thalassemia codon 44 (-C) mutation and a novel beta°-thalassemia deletion. This 67 kb deletion was characterized by restriction mapping and inverse-PCR: the 5' breakpoint is within the delta-beta-intergene region at 2,134 bp from the 3' of the delta-globin gene polyA; the 3' breakpoint is within a hsRTVL-H element at 60 kb from the 3' of the beta-globin gene. None of polymorphisms associated with high levels of gamma-globin were present in this patient. Thus, the high HbF levels in this patient derive from this novel deletion, likely because it bring close the gamma-globin gene the LTR of the RTVL-H element together with the HPFH-2 and HPFH-1 enhancer elements. The comparison with others deletion of the beta locus associated with high levels of HbF expression, suggest that the action of the recently identified gamma-globin silencing region, preserved in this patient, can be overcome by the presence of enhancer elements.