The spectrum of congenital myasthenic syndromes

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The past decade saw remarkable advances in defining the molecular and genetic basis of the congenital myasthenic syndromes. These advances would not have been possible without antecedent clinical observations, electrophysiologic analysis, and careful morphologic studies that pointed to candidate genes or proteins. For example, a kinetic abnormality of the acetylcholine receptor (AChR) detected at the single channel level pointed to a kinetic mutation in an AChR subunit; endplate AChR deficiency suggested mutations residing in an AChR subunit or in rapsyn; absence of acetylcholinesterase (AChE) from the endplate predicted mutations in the catalytic or collagen-tailed subunit of this enzyme; and a history of abrupt episodes of apnea associated with a stimulation dependent decrease of endplate potentials and currents implicated proteins concerned with ACh resynthesis or vesicular filling. Discovery of mutations in endplate-specific proteins also prompted expression studies that afforded proof of pathogenicity, provided clues for rational therapy, lead to precise structure function correlations, and highlighted functionally significant residues or molecular domains that previous systematic mutagenesis studies had failed to detect. An overview of the spectrum of the congenital myasthenic syndromes suggests that most are caused by mutations in AChR subunits, and particularly in the ε subunit. Future studies will likely uncover new types of CMS that reside in molecules governing quantal release, organization of the synaptic basal lamina, and expression and aggregation of AChR on the postsynaptic junctional folds.

Original languageEnglish (US)
Pages (from-to)347-367
Number of pages21
JournalMolecular Neurobiology
Volume26
Issue number2-3
DOIs
StatePublished - Oct 2002

Fingerprint

Congenital Myasthenic Syndromes
Cholinergic Receptors
Mutation
Proteins
Apnea
Acetylcholinesterase
Basement Membrane
Mutagenesis
Virulence
Molecular Biology
Collagen
Enzymes

Keywords

  • Acetylcholine receptor (AChR)
  • Acetylcholinesterase (AChE)
  • Choline acetyltransferase (ChAT)
  • Congenital myasthenic syndromes (CMS)
  • Neuromuscular junction
  • Patch-clamp recordings
  • Rapsyn

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

The spectrum of congenital myasthenic syndromes. / Engel, Andrew G; Ohno, Kinji; Sine, Steven M.

In: Molecular Neurobiology, Vol. 26, No. 2-3, 10.2002, p. 347-367.

Research output: Contribution to journalArticle

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