An age-dependent ABO discrepancy between mother and baby reveals a novel A^weak allele

Background: Discrepancies in ABO grouping arise due to different reasons, posing a threat to patient safety. Underlying causes include mixed-field agglutination after transfusion, chimerism, fetomaternal exchange, or inheritance of unusual alleles resulting in weak A/B antigen expression. Cord blood from the infant of a group A₂B mother typed as group O, H+. Samples were investigated to elucidate this conundrum. Study Design and Methods: Genomic DNA was analyzed by ABO genotyping and sequencing. Red blood cells (RBCs) were characterized by routine serology and flow cytometry. Glycosyltransferase structure was predicted with 3D-modeling software. Results: The mother genotyped as ABO∗A1.01/B.01, and the baby, ABO∗A1.01/O.01.01. Sequencing revealed a substitution, 311T>A, in the ABO∗A1-like allele, which predicts Ile104Asn. Flow cytometry demonstrated A antigen on the mother's RBCs equivalent to the A₂ phenotype while no A was detectable on cord RBCs. However, blood from the 11-month-old child demonstrated markedly increased A expression, likely reflecting initiation of carbohydrate chain branching. Conclusion: We unraveled a novel A^weak allele (ABO∗AW.29) in a case of apparent nonmaternity. Residue 104 is far from the catalytic site and may be involved in stabilizing the glycosyltransferase by dimerization. Our data support that the group AB mother's B-transferase stabilizes the altered A-transferase by heterodimerization, exemplifying the allelic enhancement phenomenon.