Molecular basis of the globoside-deficient P(k) blood group phenotype. Identification of four inactivating mutations in the UDP-N-acetylgalactosamine: globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase gene.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/109893
- author
- Hellberg, Åsa LU ; Poole, Joyce and Olsson, Martin L LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 277
- issue
- 33
- pages
- 29455 - 29459
- publisher
- American Society for Biochemistry and Molecular Biology
- 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
- 2016-04-01 12:36:00
- date last changed
- 2022-01-27 07:17:23
@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 = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Molecular basis of the globoside-deficient P(k) 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}}, doi = {{10.1074/jbc.M203047200}}, volume = {{277}}, year = {{2002}}, }