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Molecular Basis of the Globoside-deficient Pk Blood Group Phenotype. IDENTIFICATION OF FOUR INACTIVATING MUTATIONS IN THE UDP-N-ACETYLGALACTOSAMINE: GLOBOTRIAOSYLCERAMIDE 3-beta -N-ACETYLGALACTOSAMINYLTRANSFERASE GENE.

Hellberg, Åsa LU ; Poole, Joyce and Olsson, Martin L LU (2002) In Journal of Biological Chemistry 277(33). p.29455-29459
Abstract
The biochemistry and molecular genetics underlying the related carbohydrate blood group antigens P, P(k), and LKE in the GLOB collection and P1 in the P blood group system are complex and not fully understood. Individuals with the rare but clinically important erythrocyte phenotypes P(1)k and P(2)k lack the capability to synthesize P antigen identified as globoside, the cellular receptor for Parvo-B19 virus and some P-fimbriated Escherichia coli. As in the ABO system, naturally occurring antibodies, anti-P of the IgM and IgG class with hemolytic and cytotoxic capacity, are formed. To define the molecular basis of the P(k) phenotype we analyzed the full coding region of a candidate gene reported in 1998 as a member of the... (More)
The biochemistry and molecular genetics underlying the related carbohydrate blood group antigens P, P(k), and LKE in the GLOB collection and P1 in the P blood group system are complex and not fully understood. Individuals with the rare but clinically important erythrocyte phenotypes P(1)k and P(2)k lack the capability to synthesize P antigen identified as globoside, the cellular receptor for Parvo-B19 virus and some P-fimbriated Escherichia coli. As in the ABO system, naturally occurring antibodies, anti-P of the IgM and IgG class with hemolytic and cytotoxic capacity, are formed. To define the molecular basis of the P(k) phenotype we analyzed the full coding region of a candidate gene reported in 1998 as a member of the 3-beta-galactosyltransferase family but later shown to possess UDP-N-acetylgalactosamine:globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase or globoside synthase activity. Homozygosity for different nonsense mutations (C(202) --> T and 538insA) resulting in premature stop codons was found in blood samples from two individuals of the P(2)k phenotype. Two individuals with P(1)k and P(2)k phenotypes were homozygous for missense mutations causing amino acid substitutions (E266A or G271R) in a highly conserved region of the enzymatically active carboxyl-terminal domain in the transferase. We conclude that crucial mutations in the globoside synthase gene cause the P(k) phenotype. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
277
issue
33
pages
29455 - 29459
publisher
ASBMB
external identifiers
  • pmid:11777924
  • wos:000177509300015
  • scopus:0037119419
ISSN
1083-351X
DOI
10.1074/jbc.M203047200
language
English
LU publication?
yes
id
122708b2-304d-48b3-b84b-705ed8ab1cc8 (old id 109893)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12023287&dopt=Abstract
date added to LUP
2007-07-09 12:51:48
date last changed
2017-08-27 04:25:54
@article{122708b2-304d-48b3-b84b-705ed8ab1cc8,
  abstract     = {The biochemistry and molecular genetics underlying the related carbohydrate blood group antigens P, P(k), and LKE in the GLOB collection and P1 in the P blood group system are complex and not fully understood. Individuals with the rare but clinically important erythrocyte phenotypes P(1)k and P(2)k lack the capability to synthesize P antigen identified as globoside, the cellular receptor for Parvo-B19 virus and some P-fimbriated Escherichia coli. As in the ABO system, naturally occurring antibodies, anti-P of the IgM and IgG class with hemolytic and cytotoxic capacity, are formed. To define the molecular basis of the P(k) phenotype we analyzed the full coding region of a candidate gene reported in 1998 as a member of the 3-beta-galactosyltransferase family but later shown to possess UDP-N-acetylgalactosamine:globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase or globoside synthase activity. Homozygosity for different nonsense mutations (C(202) --> T and 538insA) resulting in premature stop codons was found in blood samples from two individuals of the P(2)k phenotype. Two individuals with P(1)k and P(2)k phenotypes were homozygous for missense mutations causing amino acid substitutions (E266A or G271R) in a highly conserved region of the enzymatically active carboxyl-terminal domain in the transferase. We conclude that crucial mutations in the globoside synthase gene cause the P(k) phenotype.},
  author       = {Hellberg, Åsa and Poole, Joyce and Olsson, Martin L},
  issn         = {1083-351X},
  language     = {eng},
  number       = {33},
  pages        = {29455--29459},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Molecular Basis of the Globoside-deficient Pk Blood Group Phenotype. IDENTIFICATION OF FOUR INACTIVATING MUTATIONS IN THE UDP-N-ACETYLGALACTOSAMINE: GLOBOTRIAOSYLCERAMIDE 3-beta -N-ACETYLGALACTOSAMINYLTRANSFERASE GENE.},
  url          = {http://dx.doi.org/10.1074/jbc.M203047200},
  volume       = {277},
  year         = {2002},
}