Familial C3 Glomerulopathy Associated with CFHR5 Mutations: Clinical Characteristics of 91 Patients in 16 Pedigrees
Gale, D. P.
Maxwell, P. H.
Cook, H. T.
Kyriacou, Kyriacos C.
Pierides, Alkis M.
Constantinou-Deltas, Constantinos D.
SourceClinical Journal of the American Society of Nephrology
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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 hematuria51 (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 CRF18 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. © 2011 by the American Society of Nephrology.
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C3 glomerulonephritis/CFHR5 nephropathy is an endemic disease in cyprus: Clinical and molecular findings in 21 families Constantinou-Deltas, Constantinos D.; Gale, D.; Cook, T.; Voskarides, Konstantinos; Athanasiou, Yiannis; Pierides, Alkis M. (2013)Microscopic haematuria is the presenting symptom of several conditions, either heritable or acquired. A well-recognized familial condition is Alport syndrome, either of X-linked or autosomal recessive inheritance, as well ...
Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis Gale, D. P.; De Jorge, E. G.; Cook, H. T.; Martinez-Barricarte, R.; Hadjisavvas, Andreas; McLean, A. G.; Pusey, C. D.; Pierides, Alkis M.; Kyriacou, Kyriacos C.; Athanasiou, Yiannis; Voskarides, Konstantinos; Constantinou-Deltas, Constantinos D.; Palmer, A.; De Cordoba, S. R.; Maxwell, P. H.; Pickering, M. C.; Frémeaux-Bacchi, V. (2010)Summary Background Complement is a key component of the innate immune system, and variation in genes that regulate its activation is associated with renal and other disease. We aimed to establish the genetic basis for a ...
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