Core C will provide centralized and curated molecular diagnostics services, cell banking and distribution functions. All three projects rely on precise and accurate definition of the deletion mutations in each of the dystrophinopathy patients under study. The recruitment of all human subjects will be through the existing Cooperative International Neuromuscular Research Group (CINRG), with an established Coordinating Center (at Children's National Medical Center), elected Executive Committee, and 24 clinical recruitment sites. The CINRG group has an ongoing federally funded natural history study of 348 Duchenne muscular dystrophy patients, and multiple ongoing additional natural history studies and clinical trials of Duchenne/Becker muscular dystrophy and limb-girdle muscular dystrophy patients. Dystrophinopathy patient samples will be received from two distinct IRB protocols. For Duchenne muscular dystrophy participants (out-of-frame mutations). Core C will originate a protocol for receipt of blood (DNA) and skin biopsies (Aim 1). The Core will establish fibroblast cultures, validate and refine the deletion mutations using arrays and nextgen sequencing, and then distribute cells to Project 2. In the second human subject protocol. Project 3 will originate the protocol for a Becker muscular dystrophy natural history study (In-frame mutations), and collect blood (DNA), skin biopsy, and optional muscle biopsy specimens from each participant in the clinical study. All participant samples will be received and banked by Core C. DNA samples from both Duchenne and Becker muscular dystrophy patients will be tested for validation and refinement of the deletion mutations/breakpoints. Skin biopsies will be cultured for fibroblasts and cell cultures sent to Projects 1 and 2 and banked. Muscle biopsies will be sent to Project 1. Innovation is through novel methods of Identification of deletion breakpoints, and application of nextgen sequencing methods (Pacific Biosciences, lllumina). Resource sharing will include entry of alt patient mutation data Into existing International databases (Leiden Muscular Dystrophy Pages;TREAT-NMD Registry). The Core will send fibroblast cultures to external Investigators upon request. The Core will also be available for application of Innovative molecular diagnostics technologies to external investigators on a collaborative basis.

National Institute of Health (NIH)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZAR1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Research Institute
United States
Zip Code
Tatem, Kathleen S; Quinn, James L; Phadke, Aditi et al. (2014) Behavioral and locomotor measurements using an open field activity monitoring system for skeletal muscle diseases. J Vis Exp :51785
Jaiswal, Jyoti K; Lauritzen, Stine P; Scheffer, Luana et al. (2014) S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells. Nat Commun 5:3795
Defour, A; Van der Meulen, J H; Bhat, R et al. (2014) Dysferlin regulates cell membrane repair by facilitating injury-triggered acid sphingomyelinase secretion. Cell Death Dis 5:e1306
Uaesoontrachoon, Kitipong; Quinn, James L; Tatem, Kathleen S et al. (2014) Long-term treatment with naproxcinod significantly improves skeletal and cardiac disease phenotype in the mdx mouse model of dystrophy. Hum Mol Genet 23:3239-49
Heier, Christopher R; Guerron, Alfredo D; Korotcov, Alexandru et al. (2014) Non-invasive MRI and spectroscopy of mdx mice reveal temporal changes in dystrophic muscle imaging and in energy deficits. PLoS One 9:e112477
Henriques-Pons, Andrea; Yu, Qing; Rayavarapu, Sree et al. (2014) Role of Toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle. Hum Mol Genet 23:2604-17
Defour, Aurelia; Sreetama, S C; Jaiswal, Jyoti K (2014) Imaging cell membrane injury and subcellular processes involved in repair. J Vis Exp :
Heier, Christopher R; Damsker, Jesse M; Yu, Qing et al. (2013) VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med 5:1569-85
Rayavarapu, Sree; Coley, William; Cakir, Erdinc et al. (2013) Identification of disease specific pathways using in vivo SILAC proteomics in dystrophin deficient mdx mouse. Mol Cell Proteomics 12:1061-73
Uaesoontrachoon, Kitipong; Cha, Hee-Jae; Ampong, Beryl et al. (2013) The effects of MyD88 deficiency on disease phenotype in dysferlin-deficient A/J mice: role of endogenous TLR ligands. J Pathol 231:199-209

Showing the most recent 10 out of 12 publications