Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction.

ABSTRACT: We describe a severe congenital myasthenic syndrome (CMS) caused by two missense mutations in the gene encoding the muscle specific receptor tyrosine kinase (MUSK). The identified MUSK mutations M605I and A727V are both located in the kinase domain of MuSK. Intracellular microelectrode recordings and microscopy studies of the neuromuscular junction conducted in an anconeus muscle biopsy revealed decreased miniature endplate potential amplitudes, reduced endplate size and simplification of secondary synaptic folds, which were consistent with postsynaptic deficit. The study also showed a striking reduction of the endplate potential quantal content, consistent with additional presynaptic failure. Expression studies in MuSK deficient myotubes revealed that A727V, which is located within the ca

SUBMITTER: Maselli RA 

PROVIDER: S-EPMC2876883 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature