(P-IG-14) Discovery of novel GYPB*04(251C,209_210dupTG) from investigation of discrepancy between S-s- serology and S-s+U+ DNA prediction

The MNS blood group system is determined by the glycophorin A (GYA) and glycophorin B (GYB) sialoglycoproteins. Antibodies directed at GYB can have varying levels of adverse effects in patients transfused with antigen-positive blood. Variants in the GYPB gene are not uncommon in individuals of African ancestry, and can make blood procurement difficult. Here we explore GPB and GYPB in a S- s- African American female.

Study

Design/Methods:

A 38-year-old African American multiparous prenatal female was subject to routine serological phenotyping and antibody identification as part of her antenatal care. Her RBCs were found to be S- s-. Commercial genotyping that incorporates multiplex PCR amplification to determine U status predicted S- s+. This discrepancy prompted further genetic testing, including Sanger sequencing of GYPB exon 1 and an in-house assay for the detection of prevalent GYPB deletions (GYPB*05N.01, GYPB*05N.02).

Results/Findings:

Serologic typing determined the patient to be S- s- with two sources of licensed anti-s. Commercial genotyping predicted S- s+ U+. Sequencing of GYPB found c.143C (which defines GYPB*s), common variant c.251C, and a novel variant c.209_210dupTG was revealed, which leads to a premature stop codon (p.71Ter), all in apparent homozygosity. The GYPB deletion assay detected GYPB*05N.01.

Conclusions:

To the best of our knowledge, allele GYPB*s(251C,209_210dupTG) has not been previously published. The premature stop codon and the s- serology are suggestive of a null phenotype (S- s- U-). This case is one more instance of the limitations of commercial genotyping assays. The patient successfully delivered her baby and did not require any units for transfusion for herself or her newborn baby.