A novel cis-AB variant allele arising from a de novo nucleotide substitution c.796A > G (p.M266V) in the B glycosyltransferase gene

Abstract

Background: Cis-AB, a rare ABO variant, is the result of a mutated ABO gene that produces a glycosyltransferase enzyme with dual A and B glycosyltransferase activity. It may lead to ABO discrepancies and a delay in establishing the blood group. To date, there have been no reports of a de novo mutation leading to a cis-AB allele. Objectives and Methods: Sequencing of the ABO gene using blood and hair follicle cells from the proposita were performed along with blood from her parents. To establish maternity and paternity, short tandem repeat (STR) analysis was also performed. The A and B enzyme activities of the novel enzyme were measured in an in vitro expression study. Results: A novel cis-AB allele arising from nucleotide substitution c.796A>G (p.M266V) in the B glycosyltransferase gene were discovered in the blood and hair follicle cells from the proposita, which was absent from her parents. In all 15 autosomal STR loci analysed, the probability of maternity and paternity were 0.999999 and 0.999989, respectively. The novel enzyme created 33.1% and 60.2% of A and B antigen compared to wild type A and B glycosyltransferases. Conclusion: A novel mechanism leading to a cis-AB allele was discovered.