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C3 Glomerulonephritis/CFHR5 Nephropathy Is an Endemic Disease in Cyprus: Clinical and Molecular Findings in 21 Families

  • Constantinos DeltasEmail author
  • Daniel Gale
  • Terence Cook
  • Konstantinos Voskarides
  • Yiannis Athanasiou
  • Alkis Pierides
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 735)

Abstract

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 as thin basement membrane nephropathy (TBMN) because of heterozygous collagen IV mutations. Even though microscopic haematuria of TBMN was long considered as a benign disease with excellent prognosis, more recent data suggest that development of chronic kidney disease (CKD) and even end-stage kidney disease (ESKD) is not a rare finding, perhaps owing to the cofounding role of modifier genes and other factors. Recent investigations in London and Cyprus culminated in the identification of another autosomal dominant condition that presents with microscopic haematuria because of heterozygous mutations in the CFHR5 gene, which apparently plays a pivotal role in the regulation of the alterative pathway of complement system, which constitutes a significant part of innate immunity in humans. Histologically, the hallmark observation is the isolated glomerular deposition of C3 complement in the absence of immune complexes. It is considered one of the C3 glomerulopathies, and it may or may not be accompanied by mild membranoproliferative glomerulonephritis. Interestingly, a single mutation has been identified so far, a duplication of exons 2–3 of the CFHR5 gene, and it has been described in patients of Greek-Cypriot descend only, perhaps originating on the Troodos mountains of Cyprus. Thus far, no patient with a mutation in this gene has been diagnosed in any other population. In Cyprus, it has been found in clusters of families in neighbouring villages in a total of 136 patients, and it constitutes a strong founder phenomenon. About 50% of patients over 50 years have progressed to CKD, and 14% of all patients progressed to ESKD. It is not quite well understood why males run a much higher risk to progress to CKD, compared to women.

Keywords

Chronic Kidney Disease Microscopic Haematuria Alport Syndrome Alternative Complement Pathway Focal Segmental Glomerular Sclerosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Constantinos Deltas
    • 1
    Email author
  • Daniel Gale
    • 2
  • Terence Cook
    • 2
  • Konstantinos Voskarides
    • 1
  • Yiannis Athanasiou
    • 3
  • Alkis Pierides
    • 4
  1. 1.Molecular Medicine Research Center and Laboratory of Molecular and Medical Genetics, Department of Biological SciencesUniversity of CyprusNicosiaCyprus
  2. 2.Imperial College Kidney and Transplant InstituteLondonUK
  3. 3.Department of NephrologyNicosia General HospitalNicosiaCyprus
  4. 4.Department of NephrologyHippocrateon HospitalNicosiaCyprus

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