Secondary Focal and Segmental Glomerulosclerosis Associated With Single-Nucleotide Polymorphisms in the Genes Encoding Complement Factor H and C3

Sanjeev Sethi; Fernando C Fervenza; Yuzhou Zhang; Richard J.H Smith

doi:10.1053/j.ajkd.2012.04.011

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Secondary Focal and Segmental Glomerulosclerosis Associated With Single-Nucleotide Polymorphisms in the Genes Encoding Complement Factor H and C3

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Secondary Focal and Segmental Glomerulosclerosis Associated With Single-Nucleotide Polymorphisms in the Genes Encoding Complement Factor H and C3

Sanjeev Sethi, Fernando C Fervenza, Yuzhou Zhang and Richard J.H Smith

American journal of kidney diseases, Vol.60(2), pp.316-321

08/2012

DOI: 10.1053/j.ajkd.2012.04.011

PMCID: PMC4433495

PMID: 22594991

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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.

Focal and segmental glomerulosclerosis (FSGS)

chronic thrombotic microangiopathy

factor H

alternative pathway of complement

Details

Title: Subtitle: Secondary Focal and Segmental Glomerulosclerosis Associated With Single-Nucleotide Polymorphisms in the Genes Encoding Complement Factor H and C3
Creators: Sanjeev Sethi - Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
Fernando C Fervenza - Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN
Yuzhou Zhang - Molecular Otolaryngology, Division of Nephrology, Carver College of Medicine, Iowa City, IA
Richard J.H Smith - Molecular Otolaryngology, Division of Nephrology, Carver College of Medicine, Iowa City, IA
Resource Type: Journal article
Publication Details: American journal of kidney diseases, Vol.60(2), pp.316-321
DOI: 10.1053/j.ajkd.2012.04.011
PMID: 22594991
PMCID: PMC4433495
NLM abbreviation: Am J Kidney Dis
ISSN: 0272-6386
eISSN: 1523-6838
Publisher: Elsevier Inc
Language: English
Date published: 08/2012
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006323802771

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