title: A hybrid CFHR3-1 gene causes familial C3 glomerulopathy.
abstract: 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.
authors.affiliation: Centre for Complement and Inflammation Research, Imperial College, London, United Kingdom.
authors.forename: Talat H
authors.initials: TH
authors.lastname: Malik
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lavin
authors.forename: Elena
authors.initials: E
authors.lastname: Goicoechea de Jorge
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Vernon
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Rose
authors.forename: Mitali P
authors.initials: MP
authors.lastname: Patel
authors.forename: Marcel
authors.initials: M
authors.lastname: de Leeuw
authors.forename: John J
authors.initials: JJ
authors.lastname: Neary
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Conlon
authors.forename: Michelle P
authors.initials: MP
authors.lastname: Winn
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Pickering
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D001798:Blood Proteins / Q000235:genetics*; D002675:Child, Preschool; D002678:Chimera / Q000235:genetics*; D003176:Complement C3 / Q000378:metabolism*; D003180:Complement C3b Inactivator Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins