© 2018 Wiley Periodicals, Inc. Introduction: Mutations in CLCN1 cause recessive or dominant forms of myotonia congenita (MC). Some mutations have been found to exhibit both patterns of inheritance but the mechanism explaining this behavior is unknown. Methods: A known recessive missense mutation, A493E, was identified in a family with dominant MC. The mutant p.A493E alone or in co-expression with wild-type (WT) ClC-1 was expressed in Xenopus oocytes. Currents were measured and biochemical assays were performed. Results: The mutant showed no significant activity and reduced total and plasma membrane (PM) protein levels. Co-expression with the mutant reduced the activity and PM levels of an engineered lower expression variant of ClC-1, whereas no effect was observed on a higher expression variant. Discussion: Our results suggest that the dominant effect of some CLCN1 mutations showing recessive or dominant inheritance patterns may be due to a dose-dependent defect in PM delivery of the WT channel. Muscle Nerve 58: 157–160, 2018.
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Gaitán-peñas, H., Armand-Ugón, M., Macaya, A., & Estévez, R. (2018). CLCN1 Myotonia congenita mutation with a variable pattern of inheritance suggests a novel mechanism of dominant myotonia. Muscle and Nerve, 58(1), 157-160. https://doi.org/10.1002/mus.26098