A novel cisAB allele with a missense variant (c.971T>C) in the ABO gene of a Brazilian family

Abstract

AbstractBackground and ObjectivesMissense variants in exon 7 of the ABO gene can lead to the formation of cisAB alleles. These alleles encode glycosyltransferases (GTs) capable of synthesizing both A and B antigens. In this study, we report the discovery of a novel cisAB allele and characterize it at molecular, protein and serological levels.Materials and MethodsBlood and DNA samples from the proband and seven relatives were examined using standard and modified ABO phenotyping, polymerase chain reaction‐restriction fragment length polymorphism and ABO gene sequencing. We assessed the impact of the p.Leu324Ser variant on the protein structure of the mutant GT using bioinformatics tools.ResultsMolecular tests revealed a c.971T>C (p.Leu324Ser) variant in the ABO gene in five of the eight individuals. This variant results in a GT that produces more A antigens and fewer B antigens. Bioinformatics analysis suggests that the amino acid substitution (p.Leu324Ser) could potentially affect enzymatic activity and specificity of the GT.ConclusionWe identified a novel cisAB allele resulting from a c.971T>C variant in the ABO gene. This variant led to the expression of an ABweak phenotype.