A Novel TRPC6 Mutation in a Family with Podocytopathy and Clinical Variability

Overview

Journal BMC Nephrol

Publisher Biomed Central

Specialty Nephrology

Date 2013 May 14

PMID 23663351

Citations 11

Authors

Amy K Mottl

Mei Lu

Catherine A Fine

Karen E Weck

Affiliations

Soon will be listed here.

Abstract

Background: Mutation in several podocyte-specific genes have been noted to result in phenotypic heterogeneity. Herein, we report a novel, autosomal dominant TRPC6 mutation in a family with disease ranging from asymptomatic minimal change disease to end-stage kidney disease.

Case Presentation: A 35 year old woman developed asymptomatic, nephrotic range proteinuria during pregnancy that did not resolve after delivery. Her mother had end-stage kidney disease of unknown etiology and her brother had asymptomatic proteinuria. Kidney biopsy revealed minimal change disease in both the proband and her brother. Genetic testing was performed in the proband and mother, revealing a novel frameshift mutation in TRPC6, D873fsX878. The proband continues to have subnephrotic range proteinuria and normal creatinine but her brother has since developed progressive chronic kidney disease.

Conclusions: The current case report underscores the heterogeneity of disease in podocytopathies and related genes. Genetic testing of podocyte genes is useful in order to understand the pathophysiologic processes underlying these overlapping diseases.

Citing Articles

Natural History and Clinicopathological Associations of TRPC6-Associated Podocytopathy.

Wooden B, Beenken A, Martinelli E, Saida K, Knob A, Ke J J Am Soc Nephrol. 2024; 36(2):274-289.

PMID: 39352759 PMC: 11801752. DOI: 10.1681/ASN.0000000501.

Gain-of-function, focal segmental glomerulosclerosis Trpc6 mutation minimally affects susceptibility to renal injury in several mouse models.

Brown B, Boekell K, Stotter B, Talbot B, Schlondorff J PLoS One. 2022; 17(8):e0272313.

PMID: 35913909 PMC: 9342776. DOI: 10.1371/journal.pone.0272313.

Characterization of a Trpc6 Transgenic Mouse Associated with Early Onset FSGS.

Canales C, Krall P, Kairath P, Perez I, Fragoso M, Carmona-Mora P Br J Med Med Res. 2021; 5(10):1198-2012.

PMID: 34012910 PMC: 8130885. DOI: 10.9734/bjmmr/2015/12493.

Two Children With Novel TRPC6 Spontaneous Missense Mutations and Atypical Phenotype: A Case Report and Literature Review.

Wang M, Wang R, He X, Yu M, Xia Z, Gao C Front Pediatr. 2020; 8:269.

PMID: 32509715 PMC: 7249804. DOI: 10.3389/fped.2020.00269.

Structural basis for pharmacological modulation of the TRPC6 channel.

Bai Y, Yu X, Chen H, Horne D, White R, Wu X Elife. 2020; 9.

PMID: 32149605 PMC: 7082128. DOI: 10.7554/eLife.53311.

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