Congenital myasthenic syndromes: Progress over the past decade

Research output: Contribution to journalArticle

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Abstract

Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic basal lamina, and postsynaptic proteins. The presynaptic CMS are associated with defects that curtail the evoked release of acetylcholine (ACh) quanta or ACh resynthesis. Defects in ACh resynthesis have now been traced to mutations in choline acetyltransferase. A basal lamina CMS is caused by mutations in the collagenic tail subunit (CoIQ) of the endplate species of acetylcholinesterase that prevent the tail subunit from associating with catalytic subunits or from becoming inserted into the synaptic basal lamina. Most postsynaptic CMS are caused by mutations in subunits of the acetylcholine receptor (AChR) that alter the kinetic properties or decrease the expression of AChR. The kinetic mutations increase or decrease the synaptic response to ACh and result in slow- and fast-channel syndromes, respectively. Most low-expressor mutations reside in the AChR ε subunit and are partially compensated by residual expression of the fetal type γ subunit. In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane.

Original languageEnglish (US)
Pages (from-to)4-25
Number of pages22
JournalMuscle and Nerve
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2003

Fingerprint

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

Keywords

  • Acetylcholine receptor
  • Acetylcholinesterase
  • Choline acetyltransferase
  • Congenital myasthenic syndromes
  • Neuromuscular junction
  • Patch-clamp recordings
  • Rapsyn

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Congenital myasthenic syndromes : Progress over the past decade. / Engel, Andrew G; Ohno, Kinji; Sine, Steven M.

In: Muscle and Nerve, Vol. 27, No. 1, 01.01.2003, p. 4-25.

Research output: Contribution to journalArticle

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