TY - JOUR
T1 - Congenital myasthenic syndromes
T2 - genetic defects of the neuromuscular junction.
AU - Ohno, Kinji
AU - Engel, Andrew G.
N1 - Funding Information:
Work in the authors’ laboratory as supported by NIH grant NS6277 (AGE) and a research from the Muscular Dystrophy Association (AGE).
PY - 2002/1
Y1 - 2002/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s11910-002-0057-7
DO - 10.1007/s11910-002-0057-7
M3 - Review article
C2 - 11898587
AN - SCOPUS:0036359457
SN - 1528-4042
VL - 2
SP - 78
EP - 88
JO - Current neurology and neuroscience reports
JF - Current neurology and neuroscience reports
IS - 1
ER -