Molecular Characterization of a β-Globin Gene Deletion of 1357 bp in a Taiwanese β-Thalassemia Carrier

Abstract

A 30-year-old male had hypochromic microcytosis and elevated Hb F and Hb A₂ levels (MCV 72.5 fL, MCH 25.2 pg, Hb F 8.9% and Hb A₂ 6.6%). Direct DNA sequencing of the entire β-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 β-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 β-globin gene) and the 3′ breakpoint was located at +810 in the second intron of the β-globin gene. A total of 1357 bp were deleted (NG_000007.3:g.69997_71353del1357). Similar to another two β-globin gene deletions reported in Black and Croatian thalassemia carriers, respectively, this deletion was the result of a non homologous breakage and reunion event.

Keywords:

• β-Thalassemia (β-thal)
• β-Globin gene deletion
• Multiplex ligation-dependent probe amplification (MLPA)
• Taiwan