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: David Beeson, Osamu Higuchi, Jackie Palace, Judy Cossins, Hayley Spearman, Susan Maxwell, John Newsom-Davis, Georgina Burke, Peter Fawcett, Masakatsu Motomura, Juliane S Müller, Hanns Lochmüller, Clarke Slater, Angela Vincent, Yuji Yamanashi
• Journal: Science (New York, N.Y.) (Science) Vol. 313 Issue 5795 Pg. 1975-8 (Sep 29 2006) ISSN: 1095-9203 [Electronic] United States
• PMID: 16917026 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DOK7 protein, human
• Muscle Proteins
• Receptors, Cholinergic
• MUSK protein, human
• Receptor Protein-Tyrosine Kinases

Topics

• Cell Line
• Cells, Cultured
• Female
• Frameshift Mutation
• Genes, Recessive
• Humans
• Male
• Muscle Fibers, Skeletal (metabolism)
• Muscle Proteins (genetics, physiology)
• Muscle Weakness (physiopathology)
• Mutation
• Myasthenic Syndromes, Congenital (genetics, pathology, physiopathology)
• Neuromuscular Junction (pathology, physiopathology)
• Pedigree
• Polymerase Chain Reaction
• Receptor Protein-Tyrosine Kinases (physiology)
• Receptors, Cholinergic (metabolism, physiology)
• Sequence Analysis, DNA
• Synaptic Transmission