(Alpha)alpha 5.3: a novel alpha(+)-thalassemia deletion with the breakpoints in the alpha 2-globin gene and in close proximity to an Alu family repeat between the psi alpha 2- and psi alpha 1-globin genes

Abstract

A novel 5.3-kb deletion of the alpha-globin gene cluster was observed in a family from Naples, Southern Italy. It removes the 5' end of the alpha 2-globin gene, causing an alpha (+)-thalassemia defect. Because of the presence of the residual 3' end of the alpha 2-globin gene, we indicated this new haplotype with the symbol (alpha)alpha 5.3. The 5' breakpoint, the first to be reported in the intergene region of the psi alpha 2- and psi alpha 1-globin genes, is located 822 bp upstream of the cap site of the psi alpha 1-gene and about 150 bp upstream of a 300-nt Alu family member. The 3' breakpoint is located in the IVS-1 nt 58 of the alpha 2-globin gene. The 5.3-kb deleted fragment shows particular characteristics: it contains four Alu sequences having long regions 80% complementary and the 5'-GGCC-3' short repeat at both ends. The sequences spanning across the breakpoints on the same strand and containing this repeat on their 3' and 5' ends, respectively, are 17 of 25 base complementary. These particular features led us to assume the formation of a multistem-loop due to the intrastrand interaction between the complementary regions as intermediate to the deletion. The unusual localization of the 5' breakpoint suggests that even the intergene region of the psi alpha 2- and psi alpha 1-globin genes may function as a deletion target.