Molecular characterization of a beta-globin gene deletion of 1357 bp in a Taiwanese beta-thalassemia carrier

A 30-year-old male had hypochromic microcytosis and elevated Hb F and Hb A(2) levels (MCV 72.5 fL, MCH 25.2 pg, Hb F 8.9% and Hb A(2) 6.6%). Direct DNA sequencing of the entire beta-globin gene revealed no anomalies. Multiplex ligation-dependent probe amplification (MLPA) showed reduced signals at probes for the promoter, 5'UTR (5' untranslated region), exon 2 and intron 2 regions of the beta-globin gene. Gap-polymerase chain reaction (gap-PCR) successfully obtained junctional fragments. Direct sequencing of the gap-PCR product revealed that the 5' breakpoint was located at -548 (relative to the Cap site of the beta-globin gene) and the 3' breakpoint was located at +810 in the second intron of the beta-globin gene. A total of 1357 bp were deleted (NG_000007.3:g.69997_71353del1357). Similar to another two beta-globin gene deletions reported in Black and Croatian thalassemia carriers, respectively, this deletion was the result of a non homologous breakage and reunion event.