Molecular identification of the novel Gγ-β hybrid hemoglobin: Hb Gγ-β Ulsan (Gγ through 13; β from 19)

Gene fusion is a very rare mechanism that produces hemoglobin variants. Less than ten types of β-like hybrid globins have been reported to date. Herein we identified the first hybrid hemoglobin between Gγ- and β-globins in a five-year-old Korean male who had thalassemia minor feature and triplication of the HBA2 gene (αα/αααα). The novel globin originated from a 27,707-base pair deletion spanning from the HBG2 to HBB gene (NG_000007.3:g.42947_70653del). Its protein sequence included 13 N-terminal amino acids from Gγ-globin, five common amino acids from Gγ- and β-globins, and 128 amino acids from β-globin (Gγ through 13; β from 19). Molecular genetic analyses characterized the hybrid DNA and RNA. Mass spectrometry and de novo protein sequencing successfully identified the fusion peptide in the hybrid hemoglobin. We named this novel hybrid Hb Gγ-β Ulsan. The novel hemoglobin constituted 37.0% of the total hemoglobin and showed reduced oxygen affinity.