Abstract
We report a patient with a slow-channel congenital myasthenic syndrome who carries a novel slow-channel mutation in the epsilon subunit of the acetylcholine receptor and has tubulofilamentous inclusion bodies, in skeletal muscle of the type observed in hereditary and sporadic inclusion body myositis. Ultrastructural analysis of a muscle specimen obtained at the age of 9 years showed an endplate myopathy typical of the slow-channel syndrome. Twenty years later, a second muscle specimen again showed the endplate myopathy as well numerous nuclear and cytoplasmic tubulofilamentous inclusion bodies. Molecular genetic studies revealed a novel valine to phenylalanine mutation (epsilonV259F) in the M2 domain of the acetylcholine receptor. Coexistence of the slow-channel syndrome with a feature of IBM has not been observed before.
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacology
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Adult
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Bungarotoxins / pharmacokinetics
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Cell Line
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DNA Mutational Analysis / methods
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Dose-Response Relationship, Drug
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Female
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Humans
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Iodine Isotopes / pharmacokinetics
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Microscopy, Electron, Transmission / methods
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Molecular Sequence Data
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Muscle, Skeletal / metabolism
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Muscle, Skeletal / pathology
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Muscle, Skeletal / ultrastructure
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Mutation*
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Myasthenic Syndromes, Congenital / complications
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Myasthenic Syndromes, Congenital / genetics*
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Myasthenic Syndromes, Congenital / pathology*
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Myositis, Inclusion Body / complications
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Myositis, Inclusion Body / genetics*
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Myositis, Inclusion Body / pathology
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Patch-Clamp Techniques / methods
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Protein Binding / drug effects
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Radioligand Assay / methods
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Receptors, Nicotinic / genetics*
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Transfection / methods
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Valine / genetics
Substances
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Bungarotoxins
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Iodine Isotopes
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Receptors, Nicotinic
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Valine
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Acetylcholine