Duke University

Michelle Winn

Jeffery M Vance

Margaret A Pericak-Vance

Rasheed A Gbadegesin

Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology and up to 20% of patients on dialysis have this diagnosis. 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. The missense mutation is a P112Q substitution, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II, and alters the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytoskeletal and structural proteins in proteinuric kidney diseases. Our findings suggest a novel mechanism for glomerular disease pathogenesis.

TRPC6 involved in glomerulonephritis

Isolated nucleotides encoding polypeptides with mutations leading to amino acid substitutions linked to hereditary kidney disease or malformation of the urinary tract are provided herein. Constructs, cells, probes and inhibitory molecules comprising these mutations are also provided and may be used in screening assays for candidate agents to treat or reverse these diseases or alternatively to provide diagnostic tests. Methods of diagnosing subjects likely to develop these diseases or to be carriers of these diseases are also provided.

Growing community of inventors

Durham, NC, United States of America

Michelle Winn