Characterization of HbH Disease Caused by Compound Heterozygotes α+-Thalassemia 3.7 kb Deletion and a Large Novel α0-Thalassemia Deletion

Abstract

We characterized here for the first time the deletional HbH disease caused by a large novel α⁰-thalassemia deletion in a 26-year-old Burmese pregnant woman. Capillary electrophoresis (CE) electropherogram revealed HbA₂ABart's H, whereas, a single-tube multiplex real-time PCR with EvaGreen and high-resolution melting (HRM) analysis for diagnosis of three common α⁰-thalassemia --^SEA, --^THAI, and --^CR deletions showed a negative result. Thus, a multiplex ligation-dependent probe amplification (MLPA) analysis was performed. The α-globin gene cluster deletion was observed spanning from upstream of HBZ to downstream of HBQ1 exon 3 covering three functional genes (HBZ, HBA2, and HBA1). This large novel deletion has not been reported previously thus we named it α⁰-thalassemia (--^BURMESE) due to its origin. In addition, deletional HbH disease is a result of compound heterozygosity for --^BURMESE/-α^3.7. Therefore, the characterization and identification of --^BURMESE is essential for genetic counseling and preventing new cases of HbH disease and Hb Bart's hydrops fetalis.

Keywords: Burmese; HbH disease; MLPA; novel deletion; α0-thalassemia.