Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by ε-AChR subunit truncating mutations
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- Sieb, J., Kraner, S., Rauch, M. et al. Hum Genet (2000) 107: 160. doi:10.1007/s004390000359
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Congenital myasthenic syndromes (CMS) are inborn disorders due to presynaptic, synaptic, or postsynaptic defects of neuromuscular transmission. Some previously described kinships with typical signs of CMS showed a marked deficiency of acetylcholine receptors (AChR) and utrophin at the neuromuscular junctions. Additionally, the end-plate ultrastructure was immature, with reduced enfolding of the postsynaptic membrane. In two such families, we found truncating mutations of the ε-AChR subunit. In family 1, both affected siblings were heteroallelic for a ε911delT and a εIVS4+1G→A mutation within the AChR ε-subunit gene (CHRNE). In the affected member of family 2, a ε1030delC mutation and a previously described εR64X mutation were found. These deleterious εAChR mutations not only result in AChR deficiency, but also affect end-plate maturation, including the formation of secondary synaptic clefts during ontogenesis.