title: Dok-7 mutations underlie a neuromuscular junction synaptopathy.
abstract: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission characterized by fatigable muscle weakness. One major subgroup of patients shows a characteristic "limb girdle" pattern of muscle weakness, in which the muscles have small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function. We showed that recessive inheritance of mutations in Dok-7, which result in a defective structure of the neuromuscular junction, is a cause of CMS with proximal muscle weakness.
authors.affiliation: Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK. dbeeson@hammer.imm.ox.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Beeson
authors.forename: Osamu
authors.initials: O
authors.lastname: Higuchi
authors.forename: Jackie
authors.initials: J
authors.lastname: Palace
authors.forename: Judy
authors.initials: J
authors.lastname: Cossins
authors.forename: Hayley
authors.initials: H
authors.lastname: Spearman
authors.forename: Susan
authors.initials: S
authors.lastname: Maxwell
authors.forename: John
authors.initials: J
authors.lastname: Newsom-Davis
authors.forename: Georgina
authors.initials: G
authors.lastname: Burke
authors.forename: Peter
authors.initials: P
authors.lastname: Fawcett
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Motomura
authors.forename: Juliane S
authors.initials: JS
authors.lastname: Müller
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Clarke
authors.initials: C
authors.lastname: Slater
authors.forename: Angela
authors.initials: A
authors.lastname: Vincent
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamanashi
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000502:physiology; D018908:Muscle Weakness / Q000503:physiopathology; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000473:pathology* / Q000503:physiopathology*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism / Q000502:physiology; D017422:Sequence Analysis, DNA; D009435:Synaptic Transmission
chemical_list: C511692:DOK7 protein, human; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases