English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/122411
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Molecular basis of factor H R1210C association with ocular and renal diseases

AuthorsRecalde, Sergio; Tortajada, Agustín ; Subías, Marta; Anter, Jauoad; Pinto, Sheila ; Rodríguez de Córdoba, Santiago
KeywordsAMD
aHUS
C3G
Complement
Factor H
R1210C mutation
hemolytic uremic syndrome
glomerular disease
Issue Date16-Sep-2015
PublisherLippincott Williams & Wilkins
CitationJASN Published online before print September 16, 2015. Recalde, Sergio et al.
AbstractThe complement factor H (FH) mutation R1210C, which was described in association with atypical hemolytic uremic syndrome (aHUS), also confers high risk of age-related macular degeneration (AMD) and associates with C3 glomerulopathy (C3G). To reveal the molecular basis of these associations and to provide insight into what determines the disease phenotype in FH-R1210C carriers, we identified FH-R1210C carriers in our aHUS, C3G, and AMD cohorts. Disease status, determined in patients and relatives, revealed an absence of AMD phenotypes in the aHUS cohort and, vice versa, a lack of renal disease in the AMD cohort. These findings were consistent with differences in the R1210C-independent overall risk for aHUS and AMD between mutation carriers developing one pathology or the other. R1210C is an unusual mutation that generates covalent complexes between FH and HSA. Using purified FH proteins and surface plasmon resonance analyses, we demonstrated that formation of these FH-HSA complexes impairs accessibility to all FH functional domains. These data suggest that R1210C is a unique C-terminal FH mutation that behaves as a partial FH deficiency, predisposing individuals to diverse pathologies with distinct underlying pathogenic mechanisms; the final disease outcome is then determined by R1210C-independent genetic risk factors.
Description27 p.-3 fig.-1 tab.-3 fig. compl.
Publisher version (URL)http://dx.doi.org/ 10.1681/ASN.2015050580
URIhttp://hdl.handle.net/10261/122411
DOI10.1681/ASN.2015050580
ISSN1046-6673
E-ISSN1533-3450
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
2015_Recalde et al_JASN.pdf1,04 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.