Familial C3 Glomerulopathy Associated with CFHR5 Mutations: Clinical Characteristics of 91 Patients in 16 Pedigrees

Yiannis Athanasiou, Konstantinos Voskarides, Daniel P. Gale, Loukas Damianou, Charalambos Patsias, Michalis Zavros, Patrick H. Maxwell, H. Terence Cook, Panayiota Demosthenous, Andreas Hadjisavvas, Kyriacos Kyriacou, Ioanna Zouvani, Alkis Pierides, Constantinos Deltas

Research output: Contribution to journalArticlepeer-review

Abstract

Background and objectives 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. Design, setting, participants, & measurements 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.

Original languageEnglish
Pages (from-to)1436-1446
Number of pages11
JournalClinical Journal of the American Society of Nephrology
Volume6
Issue number6
DOIs
Publication statusPublished - 1 Jun 2011
Externally publishedYes

Fingerprint

Dive into the research topics of 'Familial C3 Glomerulopathy Associated with CFHR5 Mutations: Clinical Characteristics of 91 Patients in 16 Pedigrees'. Together they form a unique fingerprint.

Cite this