Duke University

Jeffery M Vance

Margaret A Pericak-Vance

Michelle Winn

Stephan Zuchner

William E Kraus

Elizabeth R Hauser

Pascal J Goldschmidt

Simon G Gregory

Warren J Strittmatter

Jan J Enghild

James R Burke

Stephen Zuchner

Simon S Gregory

Methods are described for screening a subject for risk of Charcot-Marie-Tooth Disease Type 2A or for diagnosing Charcot-Marie-Tooth disease or a predisposition for developing Charcot-Marie-Tooth disease in a subject, by detecting the presence or absence of a mutation in the mitofusin gene in a biological sample collected from the subject. Methods are also described for detecting the presence of a genetic polymorphism associated with Charcot-Marie-Tooth Disease Type 2A in a sample of patient nucleic acid, by amplifying a mitofusin gene sequence in the patient nucleic acid to produce an amplification product; and identifying the presence of a Charcot-Marie-Tooth Disease Type 2A associated polymorphism in the amplification product.

Methods of detecting Charcot-Marie tooth disease type 2A

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

Methods of detecting Charcot-Marie Tooth disease type 2A

Methods of detecting charcot-marie tooth disease type 2A

The present invention provides methods of identifying a subject having an increased or decreased risk of developing cardiovascular disease, comprising:

Methods for identifying an individual at increased risk of developing coronary artery disease

The present invention provides methods of identifying a subject having an increased or decreased risk of developing cardiovascular disease, comprising: a) correlating the presence of one or more genetic markers in chromosome 3q13.31 with an increased or decreased risk of developing cardiovascular disease; and b) detecting the one or more genetic markers of step (a) in the subject, thereby identifying the subject as having an increased or decreased risk of developing cardiovascular disease. Also provided are methods of identifying subjects with cardiovascular disease as having a good or poor prognosis, as well as methods of identifying effective treatment regimens for cardiovascular disease, based on correlation with genetic markers in chromosome 3q13.31.

GAPDH binds to expanded polyglutamine regions which are found in proteins encoded by genes with CAG repeat domains, which genes cause inherited neurodegenerative disorders and are associated with certain psychiatric disorders. Therapeutic methods are based on inhibiting the binding of GAPDH to expanded polyglutamine regions. A method of screening compounds for the ability to inhibit binding of GAPDH to polyglutamine regions is described.

Method to screen compounds that affect GAPDH binding to polyglutamine

Growing community of inventors

Chapel Hill, NC, United States of America

Jeffery M Vance