Résumé :
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Dystrophin, encoded by the largest DMD human gene, is a sarcolemmal protein that is ubiquiterious and found predominantly in muscle and nervous cells. Dystrophin iscomposed of 3685 residues and is constituted by various structural regions. The largest region is the central rod domain composed by 24 repeat units comprising about85% of the residues. Each repeat is structured in triple helical coiled-coil homologous to spectrin repeats. Dystrophin interacts with a high number of partners such asdystroglycan, F-actin, lipids, nNOS and microtubules.Hundreds of mutations that conserved an open reading frame or not have been reported and lead to Becker (BMD)and Duchenne (DMD) Muscular Dystrophies respectively. DMD is a severe disease that considerably reduces patient life span while BMD is less severe with a largespectrum of severity. DMD patients have a complete deficit of dystrophin whereas BMD patients show a reduced level of internally truncated dystrophin. The observationof these truncated dystrophins is at the origin of gene therapies that aim at expressing truncated dystrophins in DMD patients. Therefore, it appears important to have agreat knowledge about the structure and function of these truncated dystrophins as observed in BMD patients.In this purposes, we developed a database with 207 inframemutations and focused on protein features. First, gene and protein data on wild type dystrophin were gathered from literature and web resources (GenBank, PDB).Then, in-frame mutations were collected from literature. In a first version of the database, we focused on the large deletions of one or more exons.For each mutation,eDystrophin provides information about the structural regions and the binding domains that are lacking in the truncated dystrophin. Structural homology models areavailable when mutation occurs in the rod domain. These models give information about consequences of mutations on protein structure and especially triple coiled-coilreconstitution of repeats. All this information can be correlated with distribution of the known BMD phenotypes when available. Comparative analysis between wild typedystrophin and mutated dystrophins are therefore available.
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