Multiple miscarriages in two sisters of Thai origin with the rare Pk phenotype caused by a novel nonsense mutation at the B3GALNT1 locus
Ricci Hagman, J. LU ; Hult, A K LU ; Westman, J S LU ; Hosseini-Maaf, B LU ; Jongruamklang, P LU ; Saipin, J ; Bejrachandra, S and Olsson, M L LU
(2019)
In Transfusion Medicine
29(3).
p.202-208
- 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... (More)
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.
(Less)
- author
- Ricci Hagman, J.
LU
; Hult, A K
LU
; Westman, J S
LU
; Hosseini-Maaf, B
LU
; Jongruamklang, P
LU
; Saipin, J
; Bejrachandra, S
and Olsson, M L
LU
- organization
- publishing date
- 2019
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Transfusion Medicine
- volume
- 29
- issue
- 3
- pages
- 7 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:29873420
- scopus:85069542369
- ISSN
- 0958-7578
- DOI
- 10.1111/tme.12544
- project
- Blood group polymorphism and its relationship to malaria susceptibility
- language
- English
- LU publication?
- yes
- id
- 71639f47-977c-4c11-903c-c6cf978f1e16
- date added to LUP
- 2019-01-31 15:59:47
- date last changed
- 2024-04-15 22:20:07
@article{71639f47-977c-4c11-903c-c6cf978f1e16,
abstract = {{<p>OBJECTIVES: To determine the genetic background underlying the Pk phenotype in two Thai sisters suffering from multiple spontaneous abortions.</p><p>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.</p><p>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.</p><p>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%.</p><p>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.</p>}},
author = {{Ricci Hagman, J. and Hult, A K and Westman, J S and Hosseini-Maaf, B and Jongruamklang, P and Saipin, J and Bejrachandra, S and Olsson, M L}},
issn = {{0958-7578}},
language = {{eng}},
number = {{3}},
pages = {{202--208}},
publisher = {{Wiley-Blackwell}},
series = {{Transfusion Medicine}},
title = {{Multiple miscarriages in two sisters of Thai origin with the rare Pk phenotype caused by a novel nonsense mutation at the B3GALNT1 locus}},
url = {{http://dx.doi.org/10.1111/tme.12544}},
doi = {{10.1111/tme.12544}},
volume = {{29}},
year = {{2019}},
}