A β-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome

Christopher M. Gomez, Ricardo A Maselli, Jason Gammack, Jose Lasalde, Shiori Tamamizu, David R. Cornblath, Mohamed Lehar, Mark McNamee, Ralph W. Kuncl

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Point mutations in the genes encoding the acetylcholine receptor (AChR) subunits have been recognized in some patients with slow-channel congenital myasthenic syndromes (CMS). Clinical, electrophysiological, and pathological differences between these patients may be due to the distinct effects of individual mutations. We report that a spontaneous mutation of the β subunit that interrupts the leucine ring of the AChR channel gate causes an eighffold increase in channel open time and a severe CMS characterized by severe endplate myopathy and extensive remodeling of the postsynaptic membrane. The pronounced abnormalities in neuromuscular synaptic architecture and function, muscle fiber damage and weakness, resulting from a single point mutation are a dramatic example of a mutation having a dominant gain of function and of hereditary excitotoxicity.

Original languageEnglish (US)
Pages (from-to)712-723
Number of pages12
JournalAnnals of Neurology
Volume39
Issue number6
DOIs
StatePublished - Jun 1996

Fingerprint

Cholinergic Receptors
Congenital Myasthenic Syndromes
Point Mutation
Mutation
Muscular Diseases
Leucine
Muscles
Membranes
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Gomez, C. M., Maselli, R. A., Gammack, J., Lasalde, J., Tamamizu, S., Cornblath, D. R., ... Kuncl, R. W. (1996). A β-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome. Annals of Neurology, 39(6), 712-723. https://doi.org/10.1002/ana.410390607

A β-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome. / Gomez, Christopher M.; Maselli, Ricardo A; Gammack, Jason; Lasalde, Jose; Tamamizu, Shiori; Cornblath, David R.; Lehar, Mohamed; McNamee, Mark; Kuncl, Ralph W.

In: Annals of Neurology, Vol. 39, No. 6, 06.1996, p. 712-723.

Research output: Contribution to journalArticle

Gomez, CM, Maselli, RA, Gammack, J, Lasalde, J, Tamamizu, S, Cornblath, DR, Lehar, M, McNamee, M & Kuncl, RW 1996, 'A β-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome', Annals of Neurology, vol. 39, no. 6, pp. 712-723. https://doi.org/10.1002/ana.410390607
Gomez, Christopher M. ; Maselli, Ricardo A ; Gammack, Jason ; Lasalde, Jose ; Tamamizu, Shiori ; Cornblath, David R. ; Lehar, Mohamed ; McNamee, Mark ; Kuncl, Ralph W. / A β-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome. In: Annals of Neurology. 1996 ; Vol. 39, No. 6. pp. 712-723.
@article{c52faaf47b404354adff1908afe7c3b9,
title = "A β-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome",
abstract = "Point mutations in the genes encoding the acetylcholine receptor (AChR) subunits have been recognized in some patients with slow-channel congenital myasthenic syndromes (CMS). Clinical, electrophysiological, and pathological differences between these patients may be due to the distinct effects of individual mutations. We report that a spontaneous mutation of the β subunit that interrupts the leucine ring of the AChR channel gate causes an eighffold increase in channel open time and a severe CMS characterized by severe endplate myopathy and extensive remodeling of the postsynaptic membrane. The pronounced abnormalities in neuromuscular synaptic architecture and function, muscle fiber damage and weakness, resulting from a single point mutation are a dramatic example of a mutation having a dominant gain of function and of hereditary excitotoxicity.",
author = "Gomez, {Christopher M.} and Maselli, {Ricardo A} and Jason Gammack and Jose Lasalde and Shiori Tamamizu and Cornblath, {David R.} and Mohamed Lehar and Mark McNamee and Kuncl, {Ralph W.}",
year = "1996",
month = "6",
doi = "10.1002/ana.410390607",
language = "English (US)",
volume = "39",
pages = "712--723",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - A β-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome

AU - Gomez, Christopher M.

AU - Maselli, Ricardo A

AU - Gammack, Jason

AU - Lasalde, Jose

AU - Tamamizu, Shiori

AU - Cornblath, David R.

AU - Lehar, Mohamed

AU - McNamee, Mark

AU - Kuncl, Ralph W.

PY - 1996/6

Y1 - 1996/6

N2 - Point mutations in the genes encoding the acetylcholine receptor (AChR) subunits have been recognized in some patients with slow-channel congenital myasthenic syndromes (CMS). Clinical, electrophysiological, and pathological differences between these patients may be due to the distinct effects of individual mutations. We report that a spontaneous mutation of the β subunit that interrupts the leucine ring of the AChR channel gate causes an eighffold increase in channel open time and a severe CMS characterized by severe endplate myopathy and extensive remodeling of the postsynaptic membrane. The pronounced abnormalities in neuromuscular synaptic architecture and function, muscle fiber damage and weakness, resulting from a single point mutation are a dramatic example of a mutation having a dominant gain of function and of hereditary excitotoxicity.

AB - Point mutations in the genes encoding the acetylcholine receptor (AChR) subunits have been recognized in some patients with slow-channel congenital myasthenic syndromes (CMS). Clinical, electrophysiological, and pathological differences between these patients may be due to the distinct effects of individual mutations. We report that a spontaneous mutation of the β subunit that interrupts the leucine ring of the AChR channel gate causes an eighffold increase in channel open time and a severe CMS characterized by severe endplate myopathy and extensive remodeling of the postsynaptic membrane. The pronounced abnormalities in neuromuscular synaptic architecture and function, muscle fiber damage and weakness, resulting from a single point mutation are a dramatic example of a mutation having a dominant gain of function and of hereditary excitotoxicity.

UR - http://www.scopus.com/inward/record.url?scp=0029900298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029900298&partnerID=8YFLogxK

U2 - 10.1002/ana.410390607

DO - 10.1002/ana.410390607

M3 - Article

C2 - 8651643

AN - SCOPUS:0029900298

VL - 39

SP - 712

EP - 723

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 6

ER -