Congenital myasthenic syndromes: genetic defects of the neuromuscular junction.

Kinji Ohno, Andrew G Engel

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic, and postsynaptic proteins. The presynaptic CMS are associated with defects that curtail the evoked release of acetylcholine (ACh) quanta or the resynthesis of ACh. Insufficient resynthesis of ACh is now known to be caused by mutations that reduce the expression, catalytic efficiency, or both of choline acetyltransferase. The synaptic CMS are caused by mutations in the collagenic tail subunit (ColQ) of the endplate species of acetylcholinesterase that prevent ColQ from associating with catalytic subunits or from insertion into the synaptic basal lamina. With one exception, postsynaptic CMS identified to date are associated with a kinetic abnormality or decreased expression of the acetylcholine receptor (AChR). Numerous mutations have now been identified in subunits of AChR that alter the kinetics or surface expression of the receptor. The kinetic mutations increase or decrease the synaptic response to ACh and result in slow- and fast-channel syndromes, respectively. Most mutations that reduce surface expression of AChR reside in the receptor's epsilon subunit and are partially compensated by residual expression of the fetal-type gamma subunit. Null mutations in both alleles of other AChR subunits are likely lethal, owing to absence of a substituting subunit.

Original languageEnglish (US)
Pages (from-to)78-88
Number of pages11
JournalCurrent Neurology and Neuroscience Reports
Volume2
Issue number1
StatePublished - Jan 2002

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Congenital Myasthenic Syndromes
Neuromuscular Junction
Cholinergic Receptors
Mutation
Acetylcholine
Choline O-Acetyltransferase
Acetylcholinesterase
Basement Membrane
Catalytic Domain
Alleles

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

Cite this

Congenital myasthenic syndromes : genetic defects of the neuromuscular junction. / Ohno, Kinji; Engel, Andrew G.

In: Current Neurology and Neuroscience Reports, Vol. 2, No. 1, 01.2002, p. 78-88.

Research output: Contribution to journalArticle

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