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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)293-301
Number of pages9
JournalMuscle and Nerve
Volume28
Issue number3
DOIs
StatePublished - Sep 1 2003

Fingerprint

Muscle Weakness
Cluster Analysis
Mutation
Congenital Myasthenic Syndromes
Genes
Cholinergic Receptors
peripheral membrane protein 43K
Electron Microscopy
Genotype
Phenotype
Biopsy
Muscles
Membranes
Proteins

Keywords

  • Acetylcholine receptor clustering
  • Congenital myasthenic syndrome
  • Rapsyn
  • Sudden infant death syndrome

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Maselli, R. A., Dunne, V., Pascual-Pascual, S. I., Bowe, C., Agius, M., Frank, R., & Wollmann, R. L. (2003). Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering. Muscle and Nerve, 28(3), 293-301. https://doi.org/10.1002/mus.10433

Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering. / Maselli, Ricardo A; Dunne, Vanessa; Pascual-Pascual, Samuel Ignacio; Bowe, Constance; Agius, Mark; Frank, Rochelle; Wollmann, Robert L.

In: Muscle and Nerve, Vol. 28, No. 3, 01.09.2003, p. 293-301.

Research output: Contribution to journalArticle

Maselli, RA, Dunne, V, Pascual-Pascual, SI, Bowe, C, Agius, M, Frank, R & Wollmann, RL 2003, 'Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering', Muscle and Nerve, vol. 28, no. 3, pp. 293-301. https://doi.org/10.1002/mus.10433
Maselli RA, Dunne V, Pascual-Pascual SI, Bowe C, Agius M, Frank R et al. Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering. Muscle and Nerve. 2003 Sep 1;28(3):293-301. https://doi.org/10.1002/mus.10433
Maselli, Ricardo A ; Dunne, Vanessa ; Pascual-Pascual, Samuel Ignacio ; Bowe, Constance ; Agius, Mark ; Frank, Rochelle ; Wollmann, Robert L. / Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering. In: Muscle and Nerve. 2003 ; Vol. 28, No. 3. pp. 293-301.
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