Mutations in GFPT1-related congenital myasthenic syndromes are associated with synaptic morphological defects and underlie a tubular aggregate myopathy with synaptopathy
| العنوان: | Mutations in GFPT1-related congenital myasthenic syndromes are associated with synaptic morphological defects and underlie a tubular aggregate myopathy with synaptopathy |
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| المؤلفون: | Claire-Sophie Davoine, Michel Fardeau, Damien Sternberg, Emmanuel Fournier, Marie-Joséphine Fontenille, Arnaud Lacour, Norma B. Romero, Elodie De Bruyckere, D. Hantai, Julien Messéant, Geoffroy Vellieux, Sophie Nicole, Tanya Stojkovic, Sylvie Sukno, Françoise Bouhour, Jeanine Koenig, S. Bauche, E. Lacène, Pascal Laforêt, Lucie Wolf, Laure Strochlic, Guy Brochier, Bruno Eymard, Aleksandra Nadaj-Pakleza, Frédéric Chevessier, Véronique Manel, Nathalie Streichenberger, Bertrand Fontaine |
| المساهمون: | Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universitätsklinikum Erlangen, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre National de la Recherche Scientifique (CNRS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de reference des maladies neuromusculaires Nantes-Angers, CHU d'Angers et Nantes, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut NeuroMyoGène (INMG), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre de référence des maladies rares neuromusculaires, Centre hospitalier de Béthune, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire |
| المصدر: | Journal of Neurology Journal of Neurology, 2017, 264 (8), pp.1791-1803. ⟨10.1007/s00415-017-8569-x⟩ Journal of Neurology, Springer Verlag, 2017, 264 (8), pp.1791-1803. ⟨10.1007/s00415-017-8569-x⟩ |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, medicine.medical_specialty, Weakness, Glycosylation, Neurology, Adolescent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], Sarcoplasm, Neuromuscular Junction, 030105 genetics & heredity, Biology, Neuromuscular junction, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, Muscle, Skeletal, Myopathy, Aged, Retrospective Studies, Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing), Myasthenic Syndromes, Congenital, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Middle Aged, Congenital myasthenic syndrome, medicine.disease, Transmembrane protein, 3. Good health, Endocrinology, medicine.anatomical_structure, Female, Synaptopathy, Neurology (clinical), medicine.symptom, 030217 neurology & neurosurgery, Follow-Up Studies, Myopathies, Structural, Congenital |
| الوصف: | International audience; Mutations in GFPT1 (glutamine-fructose-6-phosphate transaminase 1), a gene encoding an enzyme involved in glycosylation of ubiquitous proteins, cause a limb-girdle congenital myasthenic syndrome (LG-CMS) with tubular aggregates (TAs) characterized predominantly by affection of the proximal skeletal muscles and presence of highly organized and remodeled sarcoplasmic tubules in patients’ muscle biopsies. We report here the first long-term clinical follow-up of 11 French individuals suffering from LG-CMS with TAs due to GFPT1 mutations, of which nine are new. Our retrospective clinical evaluation stresses an evolution toward a myopathic weakness that occurs concomitantly to ineffectiveness of usual CMS treatments. Analysis of neuromuscular biopsies from three unrelated individuals demonstrates that the maintenance of neuromuscular junctions (NMJs) is dramatically impaired with loss of post-synaptic junctional folds and evidence of denervation–reinnervation processes affecting the three main NMJ components. Moreover, molecular analyses of the human muscle biopsies confirm glycosylation defects of proteins with reduced O-glycosylation and show reduced sialylation of transmembrane proteins in extra-junctional area. Altogether, these results pave the way for understanding the etiology of this rare neuromuscular disorder that may be considered as a “tubular aggregates myopathy with synaptopathy”. |
| وصف الملف: | application/pdf |
| تدمد: | 1432-1459 0340-5354 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5cfe8b418933426838496db9b2edb211Test https://doi.org/10.1007/s00415-017-8569-xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5cfe8b418933426838496db9b2edb211 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321459 03405354 |
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