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Dok-7 Mutations Underlie a Neuromuscular Junction Synaptopathy
David Beeson,1*Osamu Higuchi,4Jackie Palace,2Judy Cossins,1Hayley Spearman,1Susan Maxwell,1John Newsom-Davis,2Georgina Burke,1Peter Fawcett,3Masakatsu Motomura,5Juliane S. Müller,6Hanns Lochmüller,6Clarke Slater,3Angela Vincent,1Yuji Yamanashi4
Congenital myasthenic syndromes (CMSs) are a group of inheriteddisorders of neuromuscular transmission characterized by fatigablemuscle weakness. One major subgroup of patients shows a characteristic"limb girdle" pattern of muscle weakness, in which the muscleshave small, simplified neuromuscular junctions but normal acetylcholinereceptor and acetylcholinesterase function. We showed that recessiveinheritance of mutations in Dok-7, which result in a defectivestructure of the neuromuscular junction, is a cause of CMS withproximal muscle weakness.
1 Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK. 2 Department of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK. 3 School of Neurology, Neurobiology, and Psychiatry, University of Newcastle, NE2 4HH, UK. 4 Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113–8510, Japan. 5 First Department of Internal Medicine, Nagasaki University, Nagasaki 852–8501, Japan. 6 Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-University, Munich, Germany.
* To whom correspondence should be addressed. E-mail: dbeeson{at}hammer.imm.ox.ac.uk
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