Congenital myasthenic syndromes: genetic defects of the neuromuscular junction.

Kinji Ohno, Andrew G. Engel

Research output: Contribution to journalReview article

33 Scopus citations

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
DOIs
StatePublished - Jan 2002

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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