A hybrid CFHR3-1 gene causes familial C3 glomerulopathy

Controlled activation of the complement system, a key component of innate immunity, enables destruction of pathogens with minimal damage to host tissue. Complement factor H (CFH), which inhibits complement activation, and five CFH-related proteins (CFHR1-5) compose a family of structurally related m...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2012-07, Vol.23 (7), p.1155-1160
Main Authors: Malik, Talat H, Lavin, Peter J, Goicoechea de Jorge, Elena, Vernon, Katherine A, Rose, Kirsten L, Patel, Mitali P, de Leeuw, Marcel, Neary, John J, Conlon, Peter J, Winn, Michelle P, Pickering, Matthew C
Format: Article
Language:English
Subjects:
Adolescent
Adult
Biopsy
Blood Proteins - genetics
Brief Communication
Child, Preschool
Chimera - genetics
Complement C3 - metabolism
Complement C3b Inactivator Proteins - genetics
Female
Genetic Predisposition to Disease - genetics
Genotype
Glomerulonephritis, IGA - genetics
Glomerulonephritis, IGA - metabolism
Humans
Kidney - metabolism
Kidney - pathology
Male
Middle Aged
Pedigree
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Summary:Controlled activation of the complement system, a key component of innate immunity, enables destruction of pathogens with minimal damage to host tissue. Complement factor H (CFH), which inhibits complement activation, and five CFH-related proteins (CFHR1-5) compose a family of structurally related molecules. Combined deletion of CFHR3 and CFHR1 is common and confers a protective effect in IgA nephropathy. Here, we report an autosomal dominant complement-mediated GN associated with abnormal increases in copy number across the CFHR3 and CFHR1 loci. In addition to normal copies of these genes, affected individuals carry a unique hybrid CFHR3-1 gene. In addition to identifying an association between these genetic observations and complement-mediated kidney disease, these results provide insight into the protective role of the combined deletion of CFHR3 and CFHR1 in IgA nephropathy.
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.2012020166