title: Endplate structure and parameters of neuromuscular transmission in sporadic centronuclear myopathy associated with myasthenia.
abstract: Centronuclear myopathy is a pathologically diagnosed congenital myopathy. The disease genes encode proteins with membrane modulating properties (MTM1, DNM2, and BIN1) or alter excitation-contraction coupling (RYR1). Some patients also have myasthenic symptoms but electrodiagnostic and endplate studies in these are limited. A sporadic patient had fatigable weakness and a decremental EMG response. Analysis of centronuclear myopathy disease- and candidate-genes identified no mutations. Quantitative endplate electron microscopy studies revealed simplified postsynaptic regions, endplate remodeling with normal nerve terminal size, normal synaptic vesicle density, and mild acetylcholine receptor deficiency. The amplitude of the miniature endplate potential was decreased to 60% of normal. Quantal release by nerve impulse was reduced to 40% of normal due to a decreased number of releasable quanta. The safety margin of neuromuscular transmission is compromised by decreased quantal release by nerve impulse and by a reduced postsynaptic response to the released quanta.
authors.affiliation: Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Teerin
authors.initials: T
authors.lastname: Liewluck
authors.forename: Xin-Ming
authors.initials: XM
authors.lastname: Shen
authors.forename: Margherita
authors.initials: M
authors.lastname: Milone
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Engel
mesh_terms: D000328:Adult; D001706:Biopsy; D015897:Comorbidity; D004576:Electromyography; D055724:Electrophysiological Phenomena; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009045:Motor Endplate / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009157:Myasthenia Gravis / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology*; D020914:Myopathies, Structural, Congenital / Q000453:epidemiology / Q000473:pathology* / Q000503:physiopathology*; D020511:Neuromuscular Junction Diseases / Q000235:genetics / Q000503:physiopathology*; D017729:Presynaptic Terminals / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D011950:Receptors, Cholinergic / Q000378:metabolism
chemical_list: D011950:Receptors, Cholinergic