Work

Identification of a novel variant c. 761C >T on ABO*B.01 gene in ABO glycosyltransferases associated with Bweakphenotype

Year: 2023

Type: article

Abstract: Background and Objectives ABO antigens are produced from H antigen by the activity of glycosyltransferase enzyme encoded by theABOgene. Variants in theABOgene can produce a weak ABO phenotype. In this study, we identify a novelABO*BWallele and investigate the underlying mechanism leading to the Bweakphenotype. Materials and Methods The 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. Results Serological analysis confirmed the Bweakphenotype in the subject, and gene sequencing identified a novel variant c.761C>T (p.A254V) on theABO*B.01allele, resulting in aBW‐var/O.01.02genotype. In silico analysis suggested that the p.A254V variant on theBallele may reduce the stability of glycosyltransferase B (GTB), as indicated by the ΔΔGvalues. 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. Conclusion We identified a novelBWallele and demonstrated that the variant c.761C>T (p.A254V) can cause the Bweakphenotype by reducing the stability of GTB.

Source: Vox Sanguinis

DOI: 10.1111/vox.13511