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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1412228
- author
- Ståhl, Anne-Lie
LU
; Kristoffersson, Anncharlotte
; Olin, Anders
LU
; Olsson, Martin L
LU
; Roodhooft, Anne-Marie
; Proesmans, Willem
and Karpman, Diana
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Immunology
- volume
- 46
- pages
- 2236 - 2243
- publisher
- Pergamon Press Ltd.
- external identifiers
-
- wos:000267685700011
- pmid:19446882
- scopus:67349259594
- pmid:19446882
- 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
- 2016-04-04 09:06:25
- date last changed
- 2022-03-23 03:57:23
@article{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 = {{Pergamon Press Ltd.}},
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}},
doi = {{10.1016/j.molimm.2009.04.012}},
volume = {{46}},
year = {{2009}},
}