First example of hemolytic disease of the newborn caused by anti-Or and confirmation of the molecular basis of Or

Background and Objectives: The rare MNS antigen Or (MNS31) is sensitive to ficin, papain and sialidase, but partially resistant to trypsin (0.05%); th e effect of a-chymotrypsin is not known. A point mutation, 204C -> T in exo n 3 of GYPA, is associated with the Or+ phenotype. We report here the first case of hemolytic disease of the newborn (HDN) caused by anti-Or, and expa nd the information on the nature of the Or determinant. Materials and Metho ds: A woman, gravida 4, para 0, delivered a baby whose red blood cells (RBC s) were positive (2+) on the direct antiglobulin test (DAT). The mother's s erum, an eluate made from the baby's RBCs and the RBCs of the baby's father were investigated. Exon 3 of GYPA, extracted from the father's genomic DNA , was amplified and sequenced. Results: The mother's serum reacted at room temperature, 37 degreesC and on the indirect antiglobulin test with RBCs fr om the baby's father. The father's RBCs were M+N+S-s+Or+. The antibody in t he mother's serum and in the baby's eluate was identified as anti-Or. The s erum did not react with the father's RBCs treated with trypsin (180,000 U/m l), but did react with his a-chymotrypsin-treated RBCs. Amplification and s equencing of DNA from the father revealed a single point mutation, 204C -> T, in GYPA exon 3. At birth, the baby had clinical symptoms of HDN and was transfused with 36 ml of packed RBCs and received phototherapy for eight da ys. At week 11, the baby's M+N+S+s+Or+ RBCs were negative on the DAT. Concl usion: This is the first case of HDN caused by anti-Or. The observed point mutation, 204C -> T, confirms that of a previous report and predicts a chan ge of Arg (Or-) to Trp (Or+) at amino acid 31. Copyright (C) 2000 S. Karger AG. Basel.