title: A novel CFHR5 mutation associated with C3 glomerulonephritis in a Turkish girl.
abstract: C3 glomerulopathy defines a subgroup of membranoproliferative glomerulonephritis (MPGN) characterized by complement 3 (C3)-positive, immunoglobulin-negative deposits in immunofluorescence microscopy. It comprises 3 clinical conditions: dense deposit disease, C3 glomerulonephritis, and complement factor H-related 5 (CFHR5) nephropathy. Mutations in genes encoding regulatory proteins of the alternative complement pathway have been described. A 16-year-old girl was admitted to the hospital due to periorbital edema. Nephrotic syndrome accompanied by low C3 level was diagnosed. Renal biopsy showed MPGN in light microscopy, only C3 deposits in immunofluorescence microscopy, and subendothelial electron dense deposits and capillary basement membrane thickening with double contour formation in electron microscopy. C3 nephritic factor and anti complement factor H antibody were negative. Complement factor H level was normal. Genetic screening showed a novel heterozygous p.Cys269Arg variation in the CFHR5 gene without any mutation in CFH and CFI genes. Eculizumab therapy was started but was unsuccessful at 10 months of follow-up. We have identified a novel heterozygous variation in CFHR5-related nephropathy presenting with nephrotic syndrome and persistently low C3 level, thus expanding the genetic and phenotypic spectrum of the disease. Eculizumab seems to be ineffective in this subtype.
authors.affiliation: Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Nesrin
authors.initials: N
authors.lastname: Besbas
authors.forename: Bora
authors.initials: B
authors.lastname: Gulhan
authors.forename: Safak
authors.initials: S
authors.lastname: Gucer
authors.forename: Emine
authors.initials: E
authors.lastname: Korkmaz
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D003176:Complement C3 / Q000378:metabolism*; D003165:Complement System Proteins / Q000235:genetics*; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D017211:Treatment Failure
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C432223:CFHR5 protein, human; D003176:Complement C3; D003165:Complement System Proteins; C481642:eculizumab