Dok-7 mutations underlie a neuromuscular junction synaptopathy.
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.
Beeson
David
D
Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK. dbeeson@hammer.imm.ox.ac.uk
Higuchi
Osamu
O
Palace
Jackie
J
Cossins
Judy
J
Spearman
Hayley
H
Maxwell
Susan
S
Newsom-Davis
John
J
Burke
Georgina
G
Fawcett
Peter
P
Motomura
Masakatsu
M
Müller
Juliane S
JS
Lochmüller
Hanns
H
Slater
Clarke
C
Vincent
Angela
A
Yamanashi
Yuji
Y
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
C511692:DOK7 protein, human; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases