Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of muscular dystrophy. Although the genetic lesion is well described, neither the specific gene(s) nor the cellular mechanism involved in its pathophysiology are known. We propose to investigate the molecular and cellular pathophysiology of facioscapulohumeral muscular dystrophy (FSHD) utilizing the techniques of microarray analysis of skeletal muscle samples with followup biological confirmation of relevant dysregulated genes using real time RT-PCR and immunohistochemical techniques. The research proposal will test the hypotheses that in FSHD (1) critical deletion in D4Z4 heterochromatic repeats results in altered expression of adjacent 4q35 genes, and that (2) aberrant overexpression of vascular genes, either as a primary or downstream effect, is involved in the pathogenesis of this disease. The ultimate goal is to identify critical, causal disruptions in cellular function that are amenable to therapeutic intervention.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54NS048843-02
Application #
7554046
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
2
Fiscal Year
2004
Total Cost
$292,429
Indirect Cost

  Institution

Name
University of Rochester
Department
Type
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Wood, Libby; Bassez, Guillaume; Bleyenheuft, Corinne et al. (2018) Eight years after an international workshop on myotonic dystrophy patient registries: case study of a global collaboration for a rare disease. Orphanet J Rare Dis 13:155
Carrell, Samuel T; Tang, Zhenzhi; Mohr, Sabine et al. (2018) Detection of expanded RNA repeats using thermostable group II intron reverse transcriptase. Nucleic Acids Res 46:e1
Trembley, Michael A; Quijada, Pearl; Agullo-Pascual, Esperanza et al. (2018) Mechanosensitive Gene Regulation by Myocardin-Related Transcription Factors Is Required for Cardiomyocyte Integrity in Load-Induced Ventricular Hypertrophy. Circulation 138:1864-1878
Auerbach, David S; Biton, Yitschak; Polonsky, Bronislava et al. (2018) Risk of cardiac events in Long QT syndrome patients when taking antiseizure medications. Transl Res 191:81-92.e7
Sznajder, ?ukasz J; Thomas, James D; Carrell, Ellie M et al. (2018) Intron retention induced by microsatellite expansions as a disease biomarker. Proc Natl Acad Sci U S A 115:4234-4239
Jauvin, Dominic; Chrétien, Jessina; Pandey, Sanjay K et al. (2017) Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice. Mol Ther Nucleic Acids 7:465-474
Skov, Martin; Dirksen, Robert T (2017) Trojan triplets: RNA-based pathomechanisms for muscle dysfunction in Huntington's disease. J Gen Physiol 149:49-53
Pinto, Belinda S; Saxena, Tanvi; Oliveira, Ruan et al. (2017) Impeding Transcription of Expanded Microsatellite Repeats by Deactivated Cas9. Mol Cell 68:479-490.e5
Thornton, Charles A; Wang, Eric; Carrell, Ellie M (2017) Myotonic dystrophy: approach to therapy. Curr Opin Genet Dev 44:135-140
Gadalla, S M; Hilbert, J E; Martens, W B et al. (2017) Pigmentation phenotype, photosensitivity and skin neoplasms in patients with myotonic dystrophy. Eur J Neurol 24:713-718

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