title: Acute presentation and persistent glomerulonephritis following streptococcal infection in a patient with heterozygous complement factor H-related protein 5 deficiency.
abstract: Acute poststreptococcal glomerulonephritis is a common cause of acute nephritis in children. Transient hypocomplementemia and complete recovery are typical, with only a minority developing chronic disease. We describe a young girl who developed persistent kidney disease and hypocomplementemia after a streptococcal throat infection. Kidney biopsy 1 year after presentation showed isolated glomerular complement C3 deposition, membranoproliferative changes, and subendothelial, intramembranous and occasional subepithelial electron-dense deposits consistent with C3 glomerulopathy. Complement gene screening revealed a heterozygous single nucleotide insertion in exon 4 of the complement factor H-related protein 5 gene (CFHR5), resulting in a premature stop codon. This variant was not detected in 198 controls. Serum CFHR5 levels were reduced. The mother and sister of the index patient were heterozygous for the sequence variant, with no overt evidence of kidney disease. We speculate that this heterozygous CFHR5 sequence variant is a risk factor for the development of chronic kidney disease after streptococcal infection.
authors.affiliation: Centre for Complement and Inflammation Research, Imperial College, London, United Kingdom.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Vernon
authors.forename: Elena
authors.initials: E
authors.lastname: Goicoechea de Jorge
authors.forename: Angela E
authors.initials: AE
authors.lastname: Hall
authors.forename: Veronique
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Aitman
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.forename: Robert
authors.initials: R
authors.lastname: Hangartner
authors.forename: Ania
authors.initials: A
authors.lastname: Koziell
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Pickering
mesh_terms: D002648:Child; D002908:Chronic Disease; D003176:Complement C3 / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D015432:Glomerulonephritis, Membranoproliferative / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000473:pathology; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020539:Sequence Analysis, Protein; D013290:Streptococcal Infections / Q000150:complications* / Q000276:immunology
chemical_list: C432223:CFHR5 protein, human; D003176:Complement C3; D003165:Complement System Proteins