title: Current understanding of congenital myasthenic syndromes.
abstract: Investigation of congenital myasthenic syndromes (CMSs) disclosed a diverse array of molecular targets at the motor endplate. Clinical, electrophysiologic and morphologic studies paved the way for detecting CMS-related mutations in proteins such as the acetylcholine receptor, acetylcholinesterase, choline acetyltransferase, rapsyn, MuSK and Na(v)1.4. Analysis of electrophysiologic and biochemical properties of mutant proteins expressed in heterologous systems contributed crucially to defining the molecular consequences of the observed mutations and resulted in improved therapy of different CMSs. Recent crystallography studies of choline acetyltransferase and homology structural models of the acetylcholine receptor are providing further clues to how point mutations alter protein function.
authors.affiliation: Department of Neurology and Neuromuscular Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA. age@mayo.edu
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Engel
authors.forename: Steven M
authors.initials: SM
authors.lastname: Sine
mesh_terms: D000110:Acetylcholinesterase / Q000172:deficiency*; D002795:Choline O-Acetyltransferase / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006801:Humans; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital / Q000145:classification / Q000209:etiology / Q000503:physiopathology; D011950:Receptors, Cholinergic / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C051609:peripheral membrane protein 43K; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase