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

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@article{71639f47977c4c11903cc6cf978f1e16,
title = "Multiple miscarriages in two sisters of Thai origin with the rare Pk phenotype caused by a novel nonsense mutation at the B3GALNT1 locus",
abstract = "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.",
author = "{Ricci Hagman}, J. and Hult, {A K} and Westman, {J S} and B Hosseini-Maaf and P Jongruamklang and J Saipin and S Bejrachandra and Olsson, {M L}",
note = "{\textcopyright} 2018 British Blood Transfusion Society.",
year = "2019",
doi = "10.1111/tme.12544",
language = "English",
volume = "29",
pages = "202--208",
journal = "Transfusion Medicine",
issn = "0958-7578",
publisher = "Wiley-Blackwell",
number = "3",

}