Résumé :
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Congenital myopathies are inherited disorders defined by distinct structural changes in muscle fibres. Among these cytoarchitecture changes, core lesions, consisting of localized areas of mitochondria depletion and sarcomere disorganization, define traditionally two disorders: Central Core Disease (CCD) and Multi-minicore Disease (MmD), which represent jointly the most frequent form of congenital myopathy. Classically, on the basis of anatomopathological criteria such as core length and distribution, CCD and MmD have been considered independent entities with different inheritance (autosomal dominant and recessive respectively). This was supported by the identification in 1993 of the first heterozygous mutations of the ryanodine receptor type 1 gene (RYR1) in CCD. However, more recent progress in the molecular elucidation of core myopathies, and subsequent phenotype-genotype correlation studies, brought about major conceptual changes in the field. Homozygous RYR1 defects are responsible for two of the 4 MmD forms; some of these RYR1-mutated cases showed an age-related evolution of the morphological lesions, from minicores to cores, substantiating an unexpected continuity between both core myopathies. Furthermore, an overlap between core myopathies and other nosological categories was disclosed by the identification of selenoprotein N gene (SEPN1) mutations in the classical form of MmD, but also in congenital muscular dystrophy with rigid spine, Mallory-body desmin-related myopathy and, lately, congenital fibre type disproportion. Because of their clinical homogeneity, these 4 disorders are now considered as a single entity termed SEPN-related myopathy. We have recently obtained data suggesting that selenoprotein N plays a role in protecting human cells against oxidative stress. These findings help understanding the pathophysiology of core myopathies and open new therapeutic perspectives for these disorders.
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