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Science 313 (5795): 1975-1978

Copyright © 2006 by the American Association for the Advancement of Science

Dok-7 Mutations Underlie a Neuromuscular Junction Synaptopathy

David Beeson,1* Osamu Higuchi,4 Jackie Palace,2 Judy Cossins,1 Hayley Spearman,1 Susan Maxwell,1 John Newsom-Davis,2 Georgina Burke,1 Peter Fawcett,3 Masakatsu Motomura,5 Juliane S. Müller,6 Hanns Lochmüller,6 Clarke Slater,3 Angela Vincent,1 Yuji Yamanashi4

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.

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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