Two novel mutations p. L319V and p. L91P in ABO glycosyltransferases lead to Ael and Bel phenotypes

Abstract

Background - Mutations of the ABO gene  may cause the dysfunction of ABO glycosyltransferase (GT) that can result in weak ABO phenotypes. Here, we identified two novel weak ABO subgroup alleles and explored their mechanisms that caused A_el and B_el phenotypes.
Materials and methods - The ABO phenotyping and genotyping were performed by serological studies and direct DNA sequencing of the ABO gene. The role of the novel mutations were evaluated by a three-dimensional model, predicting protein structure changes, and in vitro expression assay. The total glycosyltransferase transfer capacity in supernatant of transfected cells was examined.
Results - We identified a mutation c. 955C>G (p. L319V) of A allele in an A_el subject and a mutation c. 272T>C (p. L91P) of B allele in a B_el subject. In silico analysis showed that the mutation p. L319V of the A allele and p. L91P of the B allele may change the local conformation of GT and impair the catalysis of H to A or B antigen conversion. In vitro expression study showed that mutation p. L319V impaired H to A antigen conversion, although it did not affect the expression of glycosyltransferase A.
Conclusions - Two novel “el”-type ABO subgroup alleles were identified. Both of the two novel mutations can change the local conformation of GTs and reduce protein stability. GTA mutation p. L319V can impair the conversion from H to A antigen and causes the A_el phenotype.