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

To determine the genetic background underlying the P phenotype in two Thai sisters suffering from multiple spontaneous abortions. The P antigen is carried by globoside, an abundant glycosphingolipid in the red blood cell (RBC) membrane. Inactivating mutations in the 3-β-N-acetylgalactosaminyltransfe...

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Bibliographic Details
Published in:Transfusion medicine (Oxford, England) England), 2019-06, Vol.29 (3), p.202-208
Main Authors: Ricci Hagman, J, Hult, A K, Westman, J S, Hosseini-Maaf, B, Jongruamklang, P, Saipin, J, Bejrachandra, S, Olsson, M L
Format: Article
Language:English
Subjects:
Abortion, Spontaneous - genetics
Adult
Blood Group Antigens - genetics
Codon, Nonsense
Female
Genetic Loci
Humans
N-Acetylgalactosaminyltransferases - genetics
Pregnancy
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Summary:To determine the genetic background underlying the P phenotype in two Thai sisters suffering from multiple spontaneous abortions. 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 P 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. P/P1/PX2/P 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. 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-P +, i.e. had the P 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%. 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.
ISSN:0958-7578
1365-3148
DOI:10.1111/tme.12544