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A novel mutation in the complement regulator clusterin in recurrent hemolytic uremic syndrome.

Ståhl, Anne-lie LU ; Kristoffersson, Anncharlotte; Olin, Anders LU ; Olsson, Martin L LU ; Roodhooft, Anne-Marie; Proesmans, Willem and Karpman, Diana LU (2009) In Molecular Immunology 46. p.2236-2243
Abstract
A novel heterozygous mutation in the clusterin gene, nucleotide position A1298C (glutamine>proline Q433P), was detected in exon 7 of a child with recurrent hemolytic uremic syndrome (HUS). The same mutation was found in the child's two siblings and mother but not in 120 controls. In addition, a previously described heterozygous mutation was detected in the gene encoding membrane cofactor protein (MCP) causing a 6 base-pair deletion 811-816delGACAGT in exon 6. It was found in the patient, both siblings and the father. One sibling had recovered from post-streptoccocal glomerulonephritis. Clusterin levels in the patient, siblings and parents were normal as was the migration pattern in a gel. Patient serum induced C3 and C9 deposition on... (More)
A novel heterozygous mutation in the clusterin gene, nucleotide position A1298C (glutamine>proline Q433P), was detected in exon 7 of a child with recurrent hemolytic uremic syndrome (HUS). The same mutation was found in the child's two siblings and mother but not in 120 controls. In addition, a previously described heterozygous mutation was detected in the gene encoding membrane cofactor protein (MCP) causing a 6 base-pair deletion 811-816delGACAGT in exon 6. It was found in the patient, both siblings and the father. One sibling had recovered from post-streptoccocal glomerulonephritis. Clusterin levels in the patient, siblings and parents were normal as was the migration pattern in a gel. Patient serum induced C3 and C9 deposition on normal washed platelets, and platelet activation, as detected by flow cytometry. The same phenomenon was found in serum taken from the siblings and the mother but not in the sample from the father and controls. Addition of clusterin to patient serum did not inhibit complement activation on platelets. The Q433P mutant, in isolated form, was further studied by binding to the components of the terminal complement complex. The mutant did not bind to C5b-7 that was immobilized onto a BIAcore chip, whereas wild-type clusterin did, indicating that the mutation could lead to defective inhibition of formation of the membrane attack complex under these conditions. Hemolysis of rabbit erythrocytes was inhibited by wild-type clusterin but not by the mutant. Mutated clusterin could thus not prevent assembly of the membrane attack complex on platelets and erythrocytes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Immunology
volume
46
pages
2236 - 2243
publisher
Pergamon
external identifiers
  • WOS:000267685700011
  • PMID:19446882
  • Scopus:67349259594
ISSN
1872-9142
DOI
10.1016/j.molimm.2009.04.012
language
English
LU publication?
yes
id
11f65518-2350-4f08-912f-51be157b0c9d (old id 1412228)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19446882?dopt=Abstract
date added to LUP
2009-06-03 16:29:17
date last changed
2016-10-13 04:24:01
@misc{11f65518-2350-4f08-912f-51be157b0c9d,
  abstract     = {A novel heterozygous mutation in the clusterin gene, nucleotide position A1298C (glutamine>proline Q433P), was detected in exon 7 of a child with recurrent hemolytic uremic syndrome (HUS). The same mutation was found in the child's two siblings and mother but not in 120 controls. In addition, a previously described heterozygous mutation was detected in the gene encoding membrane cofactor protein (MCP) causing a 6 base-pair deletion 811-816delGACAGT in exon 6. It was found in the patient, both siblings and the father. One sibling had recovered from post-streptoccocal glomerulonephritis. Clusterin levels in the patient, siblings and parents were normal as was the migration pattern in a gel. Patient serum induced C3 and C9 deposition on normal washed platelets, and platelet activation, as detected by flow cytometry. The same phenomenon was found in serum taken from the siblings and the mother but not in the sample from the father and controls. Addition of clusterin to patient serum did not inhibit complement activation on platelets. The Q433P mutant, in isolated form, was further studied by binding to the components of the terminal complement complex. The mutant did not bind to C5b-7 that was immobilized onto a BIAcore chip, whereas wild-type clusterin did, indicating that the mutation could lead to defective inhibition of formation of the membrane attack complex under these conditions. Hemolysis of rabbit erythrocytes was inhibited by wild-type clusterin but not by the mutant. Mutated clusterin could thus not prevent assembly of the membrane attack complex on platelets and erythrocytes.},
  author       = {Ståhl, Anne-lie and Kristoffersson, Anncharlotte and Olin, Anders and Olsson, Martin L and Roodhooft, Anne-Marie and Proesmans, Willem and Karpman, Diana},
  issn         = {1872-9142},
  language     = {eng},
  pages        = {2236--2243},
  publisher    = {ARRAY(0x675b858)},
  series       = {Molecular Immunology},
  title        = {A novel mutation in the complement regulator clusterin in recurrent hemolytic uremic syndrome.},
  url          = {http://dx.doi.org/10.1016/j.molimm.2009.04.012},
  volume       = {46},
  year         = {2009},
}