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Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering
Author(s) -
Maselli Ricardo A.,
Dunne Vanessa,
PascualPascual Samuel Ignacio,
Bowe Constance,
Agius Mark,
Frank Rochelle,
Wollmann Robert L.
Publication year - 2003
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.10433
Subject(s) - congenital myasthenic syndrome , postsynaptic potential , acetylcholine receptor , mutation , biology , phenotype , asymptomatic , medicine , receptor , genetics , endocrinology , gene
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