Résumé :
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The myotubular/centronuclear myopathies (MTM/CNM) are characterised histologically by central, often large, spaced nuclei surrounded by an area devoid of myofibrils but occupied by mitochondrial aggregates. The muscle fibres thus resemble fetal myotubes. The historical argument as to whether the X-linked form should have a separate name, myotubular myopathy, while the autosomal forms should be called centronuclear myopathies, reflects different hypotheses about whether the pathogenetic mechanism is one of defective maturation of the muscle fibres. This dispute arose long before any causative genes had been identified and the individual pathogenetic mechanisms revealed to permit objective analysis. The argument is currently being resolved. Mutations in three autosomal genes have been found to cause MTM/CNM. Heterozygous missense mutations in dynamin 2 (DNM2) and the ryanodine receptor gene (RYR1) can cause dominant forms, whilst the first gene for a recessive form to be identified is amphiphysin 2 (BIN1). Interestingly, three of the genes for MTM/CNM, including the one for the X-linked form, myotubularin (MTM1), and DNM2 and BIN1, are implicated in the same intracellular pathways. A direct functional link between the proteins encoded by the latter two has been discovered. With DNM2 mutations, onset is usually in adolescence or early adulthood, although a few infant cases have also been described. Muscle biopsies in all but the youngest patients have shown radial strands around the central nuclei. One patient with RYR1 mutation had central nuclei in her first biopsy and additional central cores in the second, and an MRI pattern consistent with that of patients with central core disease caused by RYR1 mutations. Homozygosity for missense mutations in BIN1 caused congenital or childhood onset myopathy, with severity ranging from severe congenital to only slowly progressive disease. There is further genetic heterogeneity, and at least one more gene for a recessive form remains to be identified.
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