Résumé :
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Progressive muscular dystrophies includes a set of clinical affections characterized by a progressive degenerative process that affects muscular fibers, however displaying a great phenotypic and genetic heterogeneity.In this work, 200 patients with a clinical diagnosis of muscular dystrophies of Duchenne/Becker have been explored in order to confirm/infirm this diagnosis at the molecular level and to characterize the molecular alterations involved.Our patients were analyzed at a molecular level by multiplex PCR (Chamberlain et al., 1988; Beggs et al., 1990) to search for intragenic deletions in the DMD gene coding dystrophin protein, alterations that are known to be responsible of muscular dystrophies of Duchenne (DMD) and Becker (BMD). Also, bioinformatic analysis allowed us to predict the effect of the characterized mutations.The molecular tests we used showed that about 2/3 of our patients harbored an intragenic deletion in the DMD gene, thereby underlying the high frequency of this kind of mutations in our panel. However, the extent of the deletions was variable, ranging from one to several missing exons (up to twelve). The analysis of these mutations allowed us to estimate the length of the protein product, on the basis of their effects on the reading frame of the entire coding sequence of the DMD gene.Our results underlies the high prevalence of dystrophinopathies (muscular dystrophies of Duchenne and Becker) in the Algerian population, with a precise molecular characterization of the mutations involved, also confirming the high frequency of some intragenic deletions in the DMD gene. These results are thus very useful on a diagnostic point of view, as well as in the establishment of genotype/phenotype correlations.The search for intragenic deletions in the DMD gene allowed us to confirm/infirm easily and rapidly a clinical suspicion of dystrophinopathy, thus setting up a precise molecular diagnosis, with the advantage of allowing a differential diagnosis DMD/BMD.
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