Résumé :
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Communication n° 120. Myotonic dystrophy (DM1), the most common form of inherited neuromuscular disease, is caused by a CTG repeat expansion at chromosome 19q23. Fetal muscle development is affected in patients with a congenital form of the disease, and abnormalities in muscle regeneration have been reported in patients with adult onset of the disease. The mechanisms by which the DM1 mutation affects skeletal muscles development or regeneration are unknown. In primary human DM1 satellites cell cultures, we showed that the defect of DM1 myoblasts are deficient in their ability to fuse and that this defect was proportional to the length of the CTG repeat tract. In addition, we showed that their impairment to fuse was associated with a specific reduction in myogenin gene expression. We have identified a soluble factor with a Mr < 30-KDa that is secreted by DM1 myoblasts and which blocks myogenic differentiation. This inhibitory effect was associated with a specific decrease in myogenin gene expression and was directly proportional to the length of the CTG repeat expansion. Our results suggest that the DM1 mutation triggers the expression of a soluble factor in DM1 myoblasts which inhibits muscle cell differentiation. This could have a major impact in understanding the delay in muscle development observed in the congenital form of the disease or the defects in muscle regeneration in adult patients.
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