Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering

Rapsyn, a 43‐kDa postsynaptic protein, is essential for anchoring and clustering acetylcholine receptors (AChRs) at the endplate (EP). Mutations in the rapsyn gene have been found to cause a postsynaptic congenital myasthenic syndrome (CMS). We detected six patients with CMS due to mutations in the...

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Bibliographic Details
Published in:Muscle & nerve 2003-09, Vol.28 (3), p.293-301
Main Authors: Maselli, Ricardo A., Dunne, Vanessa, Pascual-Pascual, Samuel Ignacio, Bowe, Constance, Agius, Mark, Frank, Rochelle, Wollmann, Robert L.
Format: Article
Language:English
Subjects:
acetylcholine receptor clustering
Adolescent
Biological and medical sciences
Child, Preschool
congenital myasthenic syndrome
Excitatory Postsynaptic Potentials - genetics
Female
Genetic Predisposition to Disease - genetics
Genetic Testing
Genotype
Heterozygote
Homozygote
Humans
Male
Medical sciences
Microscopy, Electron
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Muscle Proteins - deficiency
Muscle Proteins - genetics
Muscle, Skeletal - innervation
Muscle, Skeletal - pathology
Muscle, Skeletal - physiopathology
Mutation - genetics
Myasthenic Syndromes, Congenital - genetics
Myasthenic Syndromes, Congenital - metabolism
Myasthenic Syndromes, Congenital - physiopathology
Neurology
Neuromuscular Junction - genetics
Neuromuscular Junction - pathology
Neuromuscular Junction - ultrastructure
Pedigree
Phenotype
rapsyn
Receptors, Cholinergic - genetics
Receptors, Cholinergic - metabolism
Receptors, Cholinergic - ultrastructure
sudden infant death syndrome
Synaptic Membranes - genetics
Synaptic Membranes - pathology
Synaptic Membranes - ultrastructure
Synaptic Transmission - genetics
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Summary:Rapsyn, a 43‐kDa postsynaptic protein, is essential for anchoring and clustering acetylcholine receptors (AChRs) at the endplate (EP). Mutations in the rapsyn gene have been found to cause a postsynaptic congenital myasthenic syndrome (CMS). We detected six patients with CMS due to mutations in the rapsyn gene (RAPSN). In vitro studies performed in the anconeus muscle biopsies of four patients showed severe reduction of miniature EP potential amplitudes. Electron microscopy revealed various degrees of impaired development of postsynaptic membrane folds. All patients carried the N88K mutation. Three patients were homozygous for N88K and had less severe phenotypes and milder histopathologic abnormalities than the three patients who were heterozygous and carried a second mutation (either L14P, 46insC, or Y269X). Surprisingly, two N88K homozygous patients had one asymptomatic relative each who carried the same genotype, suggesting that additional genetic factors to RAPSN mutations are required for disease expression. Muscle Nerve 28: 293–301, 2003
ISSN:0148-639X
1097-4598
DOI:10.1002/mus.10433