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 3 apparently unrelated families from Campania (Southern Italy) have been investigated by using DNA restriction analysis, Inverse PCR, cloning, sequencing, Multiplex ligation-dependent probe amplification (MLPA), quantitative Real Time PCR, 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 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 micro-homology (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.