A novel A allele with 664G>A mutation identified in a family with the Am phenotype

BACKGROUND: The Am phenotype has been characterized as a weak expression of the A antigen on red blood cells but the presence of a normal quantity of the A antigen in saliva. This study describes a molecular genetic analysis of members of an Am family. STUDY DESIGN AND METHODS: The eight exon regions of the ABO genes of the Am proposita were amplified by polymerase chain reaction and cloned, and their sequences were analyzed. The alpha-1,3-N-acetylgalactosaminyltransferase (A-transferase) activities of the Am serum and the expressed Am transferase were analyzed. RESULTS: An A gene with a 664G>A mutation, which predicts an amino acid alteration of Val222Met, was identified in the Am proposita. This Am664A allele was demonstrated in other three family members with the Am phenotype. The A-transferase activity was virtually undetectable in the Am sera, and the expressed Am transferase showed weak A-transferase activity, when compared with the expressed A1 transferase, in assays that use acceptor substrates mimicking the Type 2 H structure and Type 1 H structure. CONCLUSION: A novel A allele with 664G>A mutation was demonstrated in a pedigree with the Am phenotype. The mechanism leading to the formation of the Am phenotype still awaits elucidation.