title: Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations.
abstract: Congenital myasthenic syndromes (CMS) are inborn disorders due to presynaptic, synaptic, or postsynaptic defects of neuromuscular transmission. Some previously described kinships with typical signs of CMS showed a marked deficiency of acetylcholine receptors (AChR) and utrophin at the neuromuscular junctions. Additionally, the end-plate ultrastructure was immature, with reduced enfolding of the postsynaptic membrane. In two such families, we found truncating mutations of the epsilon-AChR subunit. In family 1, both affected siblings were heteroallelic for a epsilon911delT and a epsilonIVS4+1G-->A mutation within the AChR epsilon-subunit gene (CHRNE). In the affected member of family 2, a epsilon1030delC mutation and a previously described epsilonR64X mutation were found. These deleterious epsilonAChR mutations not only result in AChR deficiency, but also affect end-plate maturation, including the formation of secondary synaptic clefts during ontogenesis.
authors.affiliation: Department of Neurology, University Hospital Bonn, Germany.
authors.forename: J P
authors.initials: JP
authors.lastname: Sieb
authors.forename: S
authors.initials: S
authors.lastname: Kraner
authors.forename: M
authors.initials: M
authors.lastname: Rauch
authors.forename: O K
authors.initials: OK
authors.lastname: Steinlein
mesh_terms: D000328:Adult; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000378:metabolism; D009045:Motor Endplate / Q000502:physiology* / Q000648:ultrastructure; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D011950:Receptors, Cholinergic / Q000235:genetics*; D049411:Utrophin
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D011950:Receptors, Cholinergic; D049411:Utrophin