Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering

Ricardo A Maselli; Vanessa Dunne; Samuel Ignacio Pascual-Pascual; Constance Bowe; Mark Agius; Rochelle Frank; Robert L Wollmann

doi:10.1002/mus.10433

Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering

Muscle Nerve. 2003 Sep;28(3):293-301. doi: 10.1002/mus.10433.

Authors

Ricardo A Maselli¹, Vanessa Dunne, Samuel Ignacio Pascual-Pascual, Constance Bowe, Mark Agius, Rochelle Frank, Robert L Wollmann

Affiliation

¹ Department of Neurology, University of California, 1515 Newton Court, Room 510, Davis, California 95616, USA. ramaselli@ucdavis.edu

PMID: 12929188
DOI: 10.1002/mus.10433

Abstract

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.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child, Preschool
Excitatory Postsynaptic Potentials / genetics
Female
Genetic Predisposition to Disease / genetics*
Genetic Testing
Genotype
Heterozygote
Homozygote
Humans
Male
Microscopy, Electron
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
Neuromuscular Junction / genetics*
Neuromuscular Junction / pathology
Neuromuscular Junction / ultrastructure
Pedigree
Phenotype
Receptors, Cholinergic / genetics
Receptors, Cholinergic / metabolism
Receptors, Cholinergic / ultrastructure
Synaptic Membranes / genetics
Synaptic Membranes / pathology
Synaptic Membranes / ultrastructure
Synaptic Transmission / genetics

Substances

Muscle Proteins
Receptors, Cholinergic
peripheral membrane protein 43K