Mechanistic diversity underlying fast channel congenital myasthenic syndromes.
A host of missense mutations in muscle nicotinic receptor subunits have been identified as the cause of congenital myasthenic syndromes (CMS). Two classes of CMS phenotypes have been identified: slow channel myasthenic syndromes (SCCMSs) and fast channel myasthenic syndromes (FCCMSs). Although both have similar phenotypic consequences, they are physiologic opposites. Expression of the FCCMS phenotype requires the missense mutation to be accompanied by a second mutation, either a null or a missense mutation, in the second allele encoding the same receptor subunit. This seemingly rare scenario has arisen with surprisingly high incidence over the past few years, and analyses of the syndromes have revealed a diverse array of mechanisms underlying the pathology. This review focuses on new mechanisms underlying the FCCMS.
Sine
Steven M
SM
Receptor Biology Laboratory, Department of Physiology and Biophysics, Mayo Medical School, Rochester, Minnesota 55905, USA. sine@mayo.edu
Wang
Hai-Long
HL
Ohno
Kinji
K
Shen
Xin-Ming
XM
Lee
Won Yong
WY
Engel
Andrew G
AG
D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020294:Myasthenic Syndromes, Congenital / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000235:genetics / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D021122:Protein Subunits; D011978:Receptors, Nicotinic