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)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Specialized Center (P50)
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Special Emphasis Panel (ZAR1)
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Children's Research Institute
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