Duke University

Vanderbilt University

Margaret A Pericak-Vance

Jeffery M Vance

Stephan Zuchner

Michelle Winn

Jonathan L Haines

Silke Schmidt

Mariano A Garcia-Blanco

Narasimhan Nagan

Jeffrey George Jones

Corey D Braastad

Simon G Gregory

Hui Zhu

Michael Hauser

Eric Postel

Allison Ashley-Koch

Stephen Zuchner

Anita Agarwal

William K Scott

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, in certain aspects, a method of identifying a subject as having an increased risk of developing multiple sclerosis, comprising detecting in the subject the presence of a nucleotide variant in the interleukin 7 receptor alpha chain gene, whereby the presence of said variant identifies the subject as having an increased risk of developing multiple sclerosis.

Methods and compositions for correlating genetic markers with multiple sclerosis

Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly whose etiology remains largely unknown. Previous studies identified chromosome 1q32 as harboring a susceptibility locus for AMD, but it was not identified. We identified a strongly associated haplotype in two independent data sets. DNA sequencing of the complement factor II gene (CFII) within this haplotype revealed a coding variant, Y402II, that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57. This identifies Complement factor II as involved in pathogenesis of AMD. This single variant alone is so common that it likely explains 43 percent of AMD in older adults. In addition, we have replicated and refined previous reports implicating a coding change in LOC387715 as the second major AMD susceptibility allele. The effect of rs10490924 appears to be completely independent of the Y402H variant in the CFH gene. The joint effect of these two susceptibility genes is consistent with a multiplicative model, and together, they may explain as much as 65% of the PAR of AMD. In contrast, the effect of rs10490924 appears to be strongly modified by cigarette smoking. Smoking and LOC387715 together may explain as much as 34% of AMD. Our data indicate that variant genotypes at rs10490924 confer a substantially larger AMD risk to cigarette smokers than non-smokers. This observation is supported by traditional case-control modeling, by ordered subset linkage analysis (OSA) incorporating pack-years of cigarette smoking as a covariate, and by family-based association analysis using a more homogeneous set of families as defined by OSA.

Genetic variants increase the risk of age-related macular degeneration

Methods of identifying polymorphisms associated with hereditary spastic paraplegia (SPG), are described. The polymorphisms associated with SPG include specific mutations in the receptor expression enhancing protein 1 (REEP1) gene. Also described are methods of diagnosis of SPG.

Identification of a novel gene underlying familial spastic paraplegia

Growing community of inventors

Chapel Hill, NC, United States of America

Margaret A Pericak-Vance