A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis by Winn Michelle P, Conlon Peter J, Lynn Kelvin L, Farrington Merry Kay, Creazzo Tony, Hawkins April F, Daskalakis Nikki, Kwan Shu Ying, Ebersviller Seth, Burchette James L, Pericak-Vance Margaret A, Howell David N, Vance Jeffery M, Rosenberg Paul B in Science (New York, N.Y.) (2005). PubMed

Abstract

Focal and segmental glomerulosclerosis (FSGS) 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 FSGS 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.

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