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dc.creatorVindas Smith, Rebeca
dc.creatorFiore, Michele
dc.creatorVásquez Cerdas, Melissa
dc.creatorCuenca Berger, Patricia
dc.creatordel Valle Carazo, Gerardo
dc.creatorLagostena, Laura
dc.creatorGaitán Peñas, Héctor
dc.creatorEstevez Povedano, Raúl
dc.creatorPush, Michael
dc.creatorMorales Montero, Fernando
dc.date.accessioned2018-02-07T14:40:33Z
dc.date.available2018-02-07T14:40:33Z
dc.date.issued2016
dc.identifier.citationhttp://onlinelibrary.wiley.com/doi/10.1002/humu.22916/fulles_ES
dc.identifier.issn1098-1004
dc.identifier.urihttp://hdl.handle.net/10669/74036
dc.description.abstractMutations in the gene coding for the skeletal muscle Cl− channel (CLCN1) lead to dominant or recessive myotonia. Here, we identified and characterized CLCN1 mutations in Costa Rican patients, who had been clinically diagnosed with myotonic dystrophy type 1 but who were negative for DM1 mutations. CLCN1 mutations c.501C>G, p.F167L and c.1235A>C, p.Q412P appeared to have recessive inheritance but patients had atypical clinical phenotypes; c.313C>T, p.R105C was found in combination with c.501C>G, p.F167L in an apparently recessive family and the c.461A>G, p.Q154R variant was associated with a less clear clinical picture. In Xenopus oocytes, none of the mutations exhibited alterations of fast or slow gating parameters or single channel conductance, and mutations p.R105C, p.Q154R, and p.F167L were indistinguishable from wild-type (WT). p.Q412P displayed a dramatically reduced current density, surface expression and exerted no dominant negative effect in the context of the homodimeric channel. Fluorescently tagged constructs revealed that p.Q412P is expressed inefficiently. Our study confirms p.F167L and p.R105C as myotonia mutations in the Costa Rican population, whereas p.Q154R may be a benign variant. p.Q412P most likely induces a severe folding defect, explaining the lack of dominance in patients and expression systems, but has WT properties once expressed in the plasma membrane.es_ES
dc.description.sponsorshipTelethon Italy/[GGP 12008]//Italyes_ES
dc.description.sponsorshipThe JEPA Foundation/[]//Italyes_ES
dc.description.sponsorshipThe Compagnia San Paolo/[]//Italyes_ES
dc.description.sponsorshipUniversidad de Costa Rica/[]/UCR/Costa Ricaes_ES
dc.description.sponsorshipMinisterio de Ciencia, Tecnología y Telecomunicaciones/[]/MICITT/Costa Ricaes_ES
dc.language.isoen_USes_ES
dc.sourceHuman Mutation Variation, Informatics and Disease, Vol. 37, (1), pp. 74-83es_ES
dc.subjectMyotoniaes_ES
dc.subjectDominant-negativees_ES
dc.subjectElectrophysiologyes_ES
dc.subjectSurface expressiones_ES
dc.subjectProtein foldinges_ES
dc.titleIdentification and Functional Characterization of CLCN1 Mutations Found in Nondystrophic Myotonia Patientses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.typeArtículo científicoes_ES
dc.identifier.doi10.1002/humu.22916
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA)es_ES
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Neurociencias (CIN)es_ES
dc.description.procedenceUCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicinaes_ES


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