3PS2.1 Inherited Ataxia Update

Abstract

acting on enzyme stability at presynaptic level. Transmission is compromised by desensitation and depolarization block at AChR at physiologic rate of stimulation in synaptic defects. Agrin stabilize laminin network being important for acetylcholinesterase (AChE) function, AChR clustering, and muscle-specific kinase (MuSK) autophosphorylation. Mutations in AChR impair ion channel gating, reducing number of AChR and cause slow channel, fast channel and AChR deficiency syndrome. AChR channel gating is impaired based probably on conformational transition by changing isomerisation between open and closed conformation. Dok7 mutations result in impaired activation of MuSK and rapsyn to concentrate AChR on junctional folds which cause small simplified and unstable neuromuscular junctions affecting both presynaptic and postsynaptic structures. MuSK mutations result in deficiency of presynaptic differentiation and postsynaptic development. Conclusions: There is no correlation of genotype and phenotype and there is no possibility to predict the severity of CMS according to known mutation. Molecular genetics is essential in differential diagnosis and understanding of the patomechanisms inducing CMS and its effective therapy.