Medicine: A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis

Michelle P. Winn, Peter J. Conlon, Kelvin L. Lynn, Merry Kay Farrington, Tony Creazzo, April F. Hawkins, Nikki Daskalakis, Shu Ying Kwan, Seth Ebersviller, James L. Burchette, Margaret A. Pericak-Vance, David N. Howell, Jeffery M. Vance, Paul B. Rosenberg

Research output: Contribution to journalArticlepeer-review

787 Scopus citations

Abstract

Focal and segmental glomerulosclerosis (FSCS) is a kidney disorder of unknown etiology, and up to 20% of patients on dialysis have been diagnosed with it. Here we show that a large family with hereditary FSCS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion-channel protein transient receptor potential cation channel 6 (TRPC6). The proline-to-glutamine substitution at position 112, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II and appears to alter the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytoskeletal and structural proteins in proteinuric kidney diseases. Our findings suggest an alternative mechanism for the pathogenesis of glomerular disease.

Original languageEnglish (US)
Pages (from-to)1801-1804
Number of pages4
JournalScience
Volume308
Issue number5729
DOIs
StatePublished - Jun 17 2005
Externally publishedYes

ASJC Scopus subject areas

  • General

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