Identification and molecular characterization of a novel 55-kb deletion recurrent in southern Italy: the Italian (G) γ((A) γδβ)°-thalassemia.

Objectives: To characterize the molecular basis of a β-thalassemia defect in subjects with mild microcytosis associated with normal Hb A2 and increased levels of Hb F.

Methods: Six subjects from three apparently unrelated families from Campania (southern Italy) have been investigated using DNA restriction analysis, inverse PCR, cloning, sequencing, multiplex ligation-dependent probe amplification (MLPA), quantitative real-time PCR, and gap-PCR.

Results: We have identified a novel 55-kb β-globin gene cluster deletion in three unrelated families: the Italian (G) γ((A) γδβ)°-thalassemia. This deletion removes most of the β-globin cluster. The 5' breakpoint was within the (A) γ-globin exon 2, and the 3' breakpoint was within a 160-bp palindrome: the breakpoint-flanking regions present a microhomology (5'-TGGG-3') that, together with the palindromic structure, may have contributed to the recombination.

Conclusions: Large deletions of β-globin gene cluster are usually found in single families. Here, we report about the novel Italian (G) γ((A) γδβ)°-thalassemia we have found in three families. Twenty years ago, the characterization of the first family was challenging, whereas that of the other families has taken advantage of nowadays techniques. The relatively high frequency of this novel deletion in southern Italy suggests that it should be tested, together with the Sicilian (δβ)°-thalassemia, in Italian and Mediterranean families with microcytosis, normal Hb A2, and increased Hb F levels.