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Published Online August 17, 2006
Science DOI: 10.1126/science.1130837

Reports

Submitted on June 5, 2006
Accepted on August 10, 2006

Dok-7 Mutations Underlie a Neuromuscular Junction Synaptopathy

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

1 Neurosciences Group, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, UK.
2 Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
3 Department of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK.
4 School of Neurology, Neurobiology, and Psychiatry, University of Newcastle, NE2 4HH, UK.
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.
David Beeson , E-mail: beeson{at}hammer.imm.ox.ac.uk

Congenital myasthenic syndromes (CMS) 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 with small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function. Here we show that recessive inheritance of mutations in Dok-7, which result in defective neuromuscular junction structure, are a cause of CMS with proximal muscle weakness.


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