PMID- 21747136
OWN - NLM
STAT- MEDLINE
DCOM- 20110825
LR  - 20110712
IS  - 1881-6096 (Print)
IS  - 1881-6096 (Linking)
VI  - 63
IP  - 7
DP  - 2011 Jul
TI  - [Genetic defects and disorders at the neuromuscular junction].
PG  - 669-78
AB  - Genetic defects in molecules expressed at the neuromuscular junction (NMJ) cause 
      congenital myasthenic syndromes (CMSs), which are characterized by muscle 
      weakness, abnormal fatigability, amyotrophy, and minor facial anomalies. Muscle 
      weakness mostly develops under 2 years but is also sometimes seen in adults. 
      Mutations identified to date include (i) muscle nicotinic acetylcholine receptor 
      (AChR) subunits, (ii) rapsyn that anchors and clusters AChRs at the neuromuscular 
      junction, (iii) agrin that is released from the nerve terminal and induces AChR 
      clustering by stimulating the downstream LRP4/MuSK/Dok-7/rapsyn/AChR pathway, 
      (iv) muscle-specific kinase (MuSK) that transmits the AChR-clustering signal from 
      agrin/LRP4 to rapsyn/AChR, (v) Dok-7 that transmits the AChR-clustering signal 
      from agrin/LRP4/MuSK to rapsyn/AChR, (vi) skeletal muscle sodium channel type 1.4 
      (Nav1.4) that spreads the depolarization potential from the endplate throughout 
      muscle fibers, (vii) collagen Q that anchors acetylcholinesterase to the synaptic 
      basal lamina, and (viii) choline acetyltransferase that resynthesizes 
      acetylcholine from recycled choline at the nerve terminal. In addition, mutations 
      in the heparin sulfate proteoglycan perlecan, which binds to many molecules 
      including collagen Q and dystroglycan, causes Schwartz-Jampel syndrome. 
      Interestingly, mutations in LRP4 cause Cenani-Lenz syndactyly syndrome but not 
      CMS. AChR, MuSK, and LRP4 are also targets of auto-antibodies in myasthenia 
      gravis. In addition, molecules at the NMJ are targets of many other disease 
      states AChRs are blocked by the snake toxin alpha-bungarotoxin and the plant 
      poison curare. The presynaptic SNARE complex is attacked by botulinum toxin. 
      Acetylcholinesterase is inhibited by the nerve gas sarin and by organophosphate 
      pesticides. This review focuses on the molecular bases underlying defects of 
      AChR, rapsyn, Nav1.4, collagen Q, and choline acetyltransferase.
FAU - Ohno, Kinji
AU  - Ohno K
AD  - Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University 
      Graduate School of Medicine, Nagoya, Japan.
LA  - jpn
PT  - English Abstract
PT  - Journal Article
PT  - Review
PL  - Japan
TA  - Brain Nerve
JT  - Brain and nerve = Shinkei kenkyu no shinpo
JID - 101299709
SB  - IM
MH  - Adult
MH  - Child, Preschool
MH  - Humans
MH  - Myasthenic Syndromes, Congenital/*genetics/physiopathology
MH  - Neural Conduction/physiology
MH  - Neuromuscular Junction/*physiopathology
EDAT- 2011/07/13 06:00
MHDA- 2011/08/27 06:00
CRDT- 2011/07/13 06:00
PHST- 2011/07/13 06:00 [entrez]
PHST- 2011/07/13 06:00 [pubmed]
PHST- 2011/08/27 06:00 [medline]
AID - 1416100947 [pii]
PST - ppublish
SO  - Brain Nerve. 2011 Jul;63(7):669-78.