title: Familial C3 glomerulopathy associated with CFHR5 mutations: clinical characteristics of 91 patients in 16 pedigrees.
abstract: OBJECTIVE
  Complement factor H and related proteins (CFHR) are key regulators of the alternative complement pathway, where loss of function mutations lead to a glomerulopathy with isolated mesangial C3 deposits without immunoglobulins. Gale et al. (12) reported on 26 patients with the first familial, hematuric glomerulopathy caused by a founder mutation in the CFHR5 gene in patients of Cypriot descent living in the United Kingdom. CFHR5 nephropathy is clinically characterized by continuous microscopic hematuria whereas some patients present with additional episodes of synpharyngitic macrohematuria, associated with infection and pyrexia. A subgroup of patients, particularly men, develop additional proteinuria, hypertension, and chronic renal disease or ESRD.
  
  
  METHODS
  We herewith expand significantly on the study by Gale et al., reporting on histologic, molecular, and clinical findings in 91 patients from 16 families with the same founder mutation.
  
  
  RESULTS
  Eighty-two patients (90%) exhibited microscopic hematuria; 51 (62%), exhibited only microscopic hematuria, whereas the remaining 31 additionally had proteinuria (38%); 28 proteinuric patients developed chronic renal failure (CRF). Among carriers of CFHR5 mutation aged >50 years, 80% of the men and 21% of the women developed CRF; 18 developed ESRD (14 men [78%], 4 women [22%]).
  
  
  CONCLUSIONS
  The diagnosis of CFHR5-related, isolated C3 glomerulopathy was established in 2009 using newly described mutation analysis after decades of follow-up with unclear diagnoses, occasionally confused with IgA nephropathy. This larger patient cohort establishes the clinical course, significant variable expressivity, and marked gender difference regarding the development of CRF and ESRD.
authors.affiliation: Department of Nephrology, Nicosia General Hospital, Nicosia, Cyprus.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Athanasiou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Voskarides
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Gale
authors.forename: Loukas
authors.initials: L
authors.lastname: Damianou
authors.forename: Charalambos
authors.initials: C
authors.lastname: Patsias
authors.forename: Michalis
authors.initials: M
authors.lastname: Zavros
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Maxwell
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.forename: Panayiota
authors.initials: P
authors.lastname: Demosthenous
authors.forename: Andreas
authors.initials: A
authors.lastname: Hadjisavvas
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Kyriacou
authors.forename: Ioanna
authors.initials: I
authors.lastname: Zouvani
authors.forename: Alkis
authors.initials: A
authors.lastname: Pierides
authors.forename: Constantinos
authors.initials: C
authors.lastname: Deltas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003176:Complement C3 / Q000032:analysis*; D003165:Complement System Proteins / Q000235:genetics*; D003535:Cyprus; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006417:Hematuria / Q000235:genetics / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000276:immunology; D008131:London; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies; D011507:Proteinuria / Q000235:genetics / Q000276:immunology; D012737:Sex Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: C432223:CFHR5 protein, human; D003176:Complement C3; D003165:Complement System Proteins