Titre :
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GNE-MYOPATHY:from beds ide features to potential therapy
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contenu dans :
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Auteurs :
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4th International Congress of Myology, 4ème colloque international de Myologie (9-13 mai 2011; Lille (France)) ;
Argov Z
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Type de document :
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Article
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Editeur :
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AFM-TELETHON, 2011
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Pages :
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p. 18
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Langues:
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Anglais
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Mots-clés :
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acide sialique
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colloque
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gène GNE
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injection intraveineuse
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liposome
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modèle animal
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mutation génétique
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myopathie distale à vacuoles bordées
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myopathie liée à GNE
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perspective thérapeutique
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phénotype
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souris
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vacuole bordée
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Résumé :
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The clinical and genetic features of hereditary inclusion body myopathy (HIBM)/ distal myopathy with rimmed vacuoles (DMRV), a disorder due to mutations in the Nacetylglucosamine epimerase/N-acetylmannosamine kinase (GNE) gene will be reviewed. Many GNE mutations were identified world-wide, including old founder ones, all resulting in the typical yet unexplained distal myopathy with quadriceps sparing and rimmed vacuoles. Emphasis will be put on the main phenotypic presentation and its diagnosis but some still-remaining enigmas related to its course will be discussed. While the defective sialic acid biosynthetic pathway that is controlled by GNE is well characterized, it is not clear whether sialylation defect is the sole cause of this myopathy. The metabolic basis and its potential therapy will be presented by I. Nishino in this symposium. Other contributing pathogenic mechanisms will be mentioned (e.g. abnormalities in GNE association with unique muscle filaments). Human therapy trial in a single patient has been initiated: results of focal delivery into muscle of normal GNE using lipo-particles (liposome) has already been published and the IV delivering has also been tried (Nemunaitis et al). An AAV8-GNE delivery system is now in its initial phase of development and shows no toxicity in mice (Mitrani-Rosenbaum et althis congress). On the verge of therapy trials, basic research using a consistent HIBM animal model with a knock in mutation and myopathic phenotype is still required not only to understand the exact pathophysiology of this myopathy but to further test therapeutic interventions.
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