TY - JOUR
T1 - Congenital myasthenic syndromes
T2 - A diverse array of molecular targets
AU - Engel, Andrew G.
AU - Ohno, Kinji
AU - Sine, Steven M.
N1 - Funding Information:
Work done in the authors’ laboratories was supported by grants from the NIH to A.G. Engel (NS-2677) and to S.M. Sine (NS-31744) and by a Muscular Dystrophy Association Grant to A.G. Engel.
PY - 2003/6
Y1 - 2003/6
N2 - The neuromuscular junction (NMJ) has served as a prototype for understanding mechanisms underlying synaptic transmission over the past 50 years. More recently, analysis of congenital myasthenic syndromes (CMS) revealed a diverse array of molecular targets and delineated their contributions to synaptic function. Clinical, electrophysiologic and morphologic studies have paved the way for detecting CMS-related mutations in proteins such as choline acetyltransferase acetylcholinesterase, the acetylcholine receptor, rapsyn, and the voltage-gated sodium channel of the Nav1.4 type. Further studies of the mutant proteins have allowed us to correlate the effects of the mutations with predicted alterations in protein structure. In this review, we focus on the symptomatology of the CMS, consider the factors that impair neuromuscular transmission, survey the mutations that have been uncovered in the different synaptic proteins, and consider the functional implications of the identified mutations.
AB - The neuromuscular junction (NMJ) has served as a prototype for understanding mechanisms underlying synaptic transmission over the past 50 years. More recently, analysis of congenital myasthenic syndromes (CMS) revealed a diverse array of molecular targets and delineated their contributions to synaptic function. Clinical, electrophysiologic and morphologic studies have paved the way for detecting CMS-related mutations in proteins such as choline acetyltransferase acetylcholinesterase, the acetylcholine receptor, rapsyn, and the voltage-gated sodium channel of the Nav1.4 type. Further studies of the mutant proteins have allowed us to correlate the effects of the mutations with predicted alterations in protein structure. In this review, we focus on the symptomatology of the CMS, consider the factors that impair neuromuscular transmission, survey the mutations that have been uncovered in the different synaptic proteins, and consider the functional implications of the identified mutations.
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U2 - 10.1023/B:NEUR.0000020639.22895.28
DO - 10.1023/B:NEUR.0000020639.22895.28
M3 - Review article
C2 - 15034283
AN - SCOPUS:3042617450
SN - 0300-4864
VL - 32
SP - 1017
EP - 1037
JO - Journal of Neurocytology
JF - Journal of Neurocytology
IS - 5-8
ER -