Multiple miscarriages in two sisters of Thai origin with the rare P^k phenotype caused by a novel nonsense mutation at the B3GALNT1 locus

• Main Authors: J. Ricci Hagman, A. K. Hult, J. S. Westman, B. Hosseini-Maaf, P. Jongruamklang, J. Saipin, S. Bejrachandra, M. L. Olsson
• Other Authors: Region Skåne
• Format: Article
• Published: 2020
• Subjects: Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/51620
• Institution: Mahidol University

© 2018 British Blood Transfusion Society Objectives: To determine the genetic background underlying the Pk phenotype in two Thai sisters suffering from multiple spontaneous abortions. Background: The P antigen is carried by globoside, an abundant glycosphingolipid in the red blood cell (RBC) membrane. Inactivating mutations in the 3-β-N-acetylgalactosaminyltransferase gene (B3GALNT1) give rise to the rare Pk phenotype, which lack the P and PX2 antigens. Consequently, naturally occurring anti-P may cause recurrent miscarriages following the cytotoxic attack of the globoside-rich fetal portion of the placenta. Methods/Materials: P/P1/PX2/Pk antigens on RBCs and their corresponding antibodies were detected by haemagglutination and flow cytometry. The B3GALNT1 coding region was sequenced, and an allele-specific polymerase chain reaction (PCR) was developed. Results: The two sisters had suffered 8 and 11 miscarriages, most of which occurred in the first trimester. Anti-P and anti-PX2 were identified in their plasmas, and the RBCs typed as P–PX2–Pk+, i.e. had the Pk phenotype. Sequencing revealed homozygosity for a nonsense mutation, c.420T>G, in B3GALNT1. This substitution introduces a premature stop codon, p.Tyr140Ter, which is predicted to abolish enzymatic activity. Screening of 384 Thai donors indicated an allele frequency of 0·13%. Conclusion: We describe a novel nonsense mutation (c.420T>G) in B3GALNT1 (GLOB*01N·13), which was added to the 12 alleles already known in the GLOB system.