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Animal Models of the Neuromuscular Junction, Vitally Informative for Understanding Function and the Molecular Mechanisms of Congenital Myasthenic Syndromes
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Int. J. Mol. Sci. 2018, 19(6), 1677; https://doi.org/10.3390/ijms19061677

The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes

1
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK
2
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Hospital, Oxford OX3 9DS, UK
*
Author to whom correspondence should be addressed.
Received: 23 April 2018 / Revised: 17 May 2018 / Accepted: 21 May 2018 / Published: 5 June 2018
(This article belongs to the Special Issue The Neuromuscular Synapse in Health and Disease)
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Abstract

Congenital myasthenic syndromes (CMS) are genetic disorders characterised by impaired neuromuscular transmission. This review provides an overview on CMS and highlights recent advances in the field, including novel CMS causative genes and improved therapeutic strategies. CMS due to mutations in SLC5A7 and SLC18A3, impairing the synthesis and recycling of acetylcholine, have recently been described. In addition, a novel group of CMS due to mutations in SNAP25B, SYT2, VAMP1, and UNC13A1 encoding molecules implicated in synaptic vesicles exocytosis has been characterised. The increasing number of presynaptic CMS exhibiting CNS manifestations along with neuromuscular weakness demonstrate that the myasthenia can be only a small part of a much more extensive disease phenotype. Moreover, the spectrum of glycosylation abnormalities has been increased with the report that GMPPB mutations can cause CMS, thus bridging myasthenic disorders with dystroglycanopathies. Finally, the discovery of COL13A1 mutations and laminin α5 deficiency has helped to draw attention to the role of extracellular matrix proteins for the formation and maintenance of muscle endplates. The benefit of β2-adrenergic agonists alone or combined with pyridostigmine or 3,4-Dyaminopiridine is increasingly being reported for different subtypes of CMS including AChR-deficiency and glycosylation abnormalities, thus expanding the therapeutic repertoire available. View Full-Text
Keywords: congenital myasthenic syndromes; neuromuscular junction; neuromuscular transmission; presynaptic CMS; COL13A1; SNARE complex; N-glycosylation pathway; GMPPB; β2-adrenergic agonists congenital myasthenic syndromes; neuromuscular junction; neuromuscular transmission; presynaptic CMS; COL13A1; SNARE complex; N-glycosylation pathway; GMPPB; β2-adrenergic agonists
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Rodríguez Cruz, P.M.; Palace, J.; Beeson, D. The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes. Int. J. Mol. Sci. 2018, 19, 1677.

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