Identification of a novel variant c.761C>T on ABOB.01 gene in ABO glycosyltransferases associated with Bweak phenotype

Background and ObjectivesABO antigens are produced from H antigen by the activity of glycosyltransferase enzyme encoded by the ABO gene. Variants in the ABO gene can produce a weak ABO phenotype. In this study, we identify a novel ABO*BW allele and investigate the underlying mechanism leading to the Bweak phenotype.Materials and MethodsThe ABO phenotype and genotype of the sample were determined using serological and direct DNA sequencing methods. We assessed the impact of the novel variant by three‐dimensional modelling to predict protein stability changes (ΔΔG), and carried out an in vitro expression assay. The total glycosyltransferase transfer capacity in the supernatant of transfected cells was also examined.ResultsSerological analysis confirmed the Bweak phenotype in the subject, and gene sequencing identified a novel variant c.761C>T (p.A254V) on the ABO*B.01 allele, resulting in a BW‐var/O.01.02 genotype. In silico analysis suggested that the p.A254V variant on the B allele may reduce the stability of glycosyltransferase B (GTB), as indicated by the ΔΔG values. In vitro expression studies showed that the variant p.A254V impaired H to B antigen conversion, although it did not affect the expression of GTB.ConclusionWe identified a novel BW allele and demonstrated that the variant c.761C>T (p.A254V) can cause the Bweak phenotype by reducing the stability of GTB.