Secondary focal and segmental glomerulosclerosis associated with single-nucleotide polymorphisms in the genes encoding complement factor H and C3

Sanjeev M Sethi, Fernando Custodio Fervenza, Yuzhou Zhang, Richard J H Smith

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21 Citations (Scopus)

Abstract

Genetic causes of focal and segmental glomerulosclerosis (FSGS) typically involve mutations and allele variants of genes expressed in podocytes or, more rarely, glomerular basement membranes. In this report, we describe a 60-year-old woman with chronic kidney disease whose kidney biopsy showed FSGS. Immunoglobulins and C3 were undetectable in immunofluorescence studies. Electron microscopy showed subendothelial fluffy granular material with occasional double-contour formation suggestive of capillary wall injury and prompting work-up for a prothrombotic state. Evaluation of the alternative pathway of complement showed a novel polymorphism in short consensus repeat (SCR) 12 of complement factor H (CFH; c.2195C>T, p.Thr732Met) and a previously reported but largely uncharacterized polymorphism in complement factor C3 (c.463A>C, p.Lys155Gln). Dysregulation of the alternative pathway is associated with atypical hemolytic syndrome and dense deposit disease, but heretofore has not been associated with FSGS. This case highlights the expanding spectrum of complement-mediated glomerular disease and shows that FSGS with features of capillary wall injury should prompt evaluation for abnormalities in the alternative pathway. This case also expands the list of genetic polymorphisms that can be associated with an FSGS phenotype.

Original languageEnglish (US)
Pages (from-to)316-321
Number of pages6
JournalAmerican Journal of Kidney Diseases
Volume60
Issue number2
DOIs
StatePublished - Aug 2012

Fingerprint

Complement Factor H
Focal Segmental Glomerulosclerosis
Single Nucleotide Polymorphism
Genes
Membranoproliferative Glomerulonephritis
Alternative Complement Pathway
Podocytes
Glomerular Basement Membrane
Complement C3
Wounds and Injuries
Genetic Polymorphisms
Chronic Renal Insufficiency
Fluorescent Antibody Technique
Immunoglobulins
Electron Microscopy
Alleles
Phenotype
Kidney
Biopsy
Mutation

Keywords

  • alternative pathway of complement
  • C3
  • chronic thrombotic microangiopathy
  • factor H
  • Focal and segmental glomerulosclerosis (FSGS)

ASJC Scopus subject areas

  • Nephrology

Cite this

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title = "Secondary focal and segmental glomerulosclerosis associated with single-nucleotide polymorphisms in the genes encoding complement factor H and C3",
abstract = "Genetic causes of focal and segmental glomerulosclerosis (FSGS) typically involve mutations and allele variants of genes expressed in podocytes or, more rarely, glomerular basement membranes. In this report, we describe a 60-year-old woman with chronic kidney disease whose kidney biopsy showed FSGS. Immunoglobulins and C3 were undetectable in immunofluorescence studies. Electron microscopy showed subendothelial fluffy granular material with occasional double-contour formation suggestive of capillary wall injury and prompting work-up for a prothrombotic state. Evaluation of the alternative pathway of complement showed a novel polymorphism in short consensus repeat (SCR) 12 of complement factor H (CFH; c.2195C>T, p.Thr732Met) and a previously reported but largely uncharacterized polymorphism in complement factor C3 (c.463A>C, p.Lys155Gln). Dysregulation of the alternative pathway is associated with atypical hemolytic syndrome and dense deposit disease, but heretofore has not been associated with FSGS. This case highlights the expanding spectrum of complement-mediated glomerular disease and shows that FSGS with features of capillary wall injury should prompt evaluation for abnormalities in the alternative pathway. This case also expands the list of genetic polymorphisms that can be associated with an FSGS phenotype.",
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