title: Genes at the junction--candidates for congenital myasthenic syndromes.
abstract: The neuromuscular junction is the site of several myasthenic (mys, muscle; aesthenia, weakness) disorders of autoimmune and genetic origin. The acquired autoimmune conditions are mainly adult-onset and caused by antibodies to specific neuronal and muscle ion channels, but can occur neonatally due to placental transfer of maternal antibodies. This review focuses on the rarer genetic conditions, called congenital myasthenic syndromes (CMS), that often present at birth. Mutations have yet to be characterized for familial infantile myasthenia, acetylcholinesterase deficiency and ACh-receptor deficiency; but genes encoding both structural and functional NMJ protiens should be considered. Other syndromes have recently been shown to involve defects in the functioning of the ACh receptor itself. In particular, eight different mutations have been reported in cases of the slow channel syndrome, a dominant condition associated with point mutations that generate single amino acid changes within the ACh receptor and result in prolonged channel activations. These investigations are providing new insights into the structure and function of the ACh receptor. Further studies of CMS should pave the way for analysis and treatment of disorders involving other synapses in the peripheral and central nervous system.
authors.affiliation: Dept of Clinical Neurology, University of Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Vincent
authors.forename: C
authors.initials: C
authors.lastname: Newland
authors.forename: R
authors.initials: R
authors.lastname: Croxen
authors.forename: D
authors.initials: D
authors.lastname: Beeson
mesh_terms: D000110:Acetylcholinesterase / Q000172:deficiency; D000818:Animals; D006801:Humans; D009157:Myasthenia Gravis / Q000151:congenital* / Q000235:genetics*; D009469:Neuromuscular Junction / Q000503:physiopathology*; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000172:deficiency / Q000235:genetics
chemical_list: D011950:Receptors, Cholinergic; D000110:Acetylcholinesterase