A novel GYPB-A-B hybrid gene responsible for Ss and MN typing discrepancies

Transfusion support of S-s- patients is very challenging but can now be alleviated by genotyping mutations in the GYPB gene to predict their U- or U+(var) phenotype. However, the phenotype predicted by genotyping does not always correspond to the observed phenotype of red blood cells (RBCs), which requires further investigation to avoid such a typing discrepancy in the future. In this study, we elucidated the case of an S-s- female patient of African origin who was predicted to be S+s- by our genotyping platform.

Long-range polymerase chain reaction (PCR) amplification and extended Sanger sequencing were required.

The Ss typing discrepancy in the proband resulted from a converted GYPB allele that encodes neither S nor s due to the replacement of Exon B4 of GYPB by the homologous Exon A4 of GYPA. In this novel GYPB-A-B hybrid gene, the GYPA segment actually starts just downstream of Exon B2, causing a MN typing discrepancy too. While the proband's RBCs were M+N-, the genotyping predicted the M+N+ phenotype.

The reported GYPB-A-B hybrid gene constitutes a limitation for the accurate prediction of the MN and Ss phenotypes by current genotyping methods. A PCR assay was therefore developed to detect its presence.