Identification of a New δ chain hemoglobin Variant, Hb A2-Malay [δ46(CD5)Gly > Arg, HBD : C.139G > C;316-443A > G]

We report a novel δ-chain hemoglobin (Hb) variant, designated Hb A2-Malay [HBD:c.139G > C;316-443A > G], identified in 19 Malaysian Malay individuals. This variant was consistently observed in both Capillary Electrophoresis (CE) Zone 1 and High-Performance Liquid Chromatography (HPLC) S-window analyses. Sanger sequencing revealed a new G > C substitution at the first base of codon 46 within the HBD gene, leading to a glycine to arginine amino acid change. Additionally, a cis-acting polymorphism, an A to G substitution at intron II position 456, was genotyped in all carriers. Routine genetic testing for common α-thalassemia, using Gap-PCR and Amplification Refractory Mutation System, was also performed. Four carriers exhibiting similar hematological indices were found to have a concomitant heterozygous -α3.7 mutation. Furthermore, three βE carriers demonstrated higher Zone 1 and S-window percentages.