A PTG variant contributes to a milder phenotype in Lafora disease

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dc.contributor.author Guerrero, Rosa
dc.contributor.author Vérnia, Santiago
dc.contributor.author Sanz, Raúl
dc.contributor.author Abreu-Rodríguez, Irene
dc.contributor.author Almaraz, Carmen
dc.contributor.author García-Hoyos, María
dc.contributor.author Michelucci, Roberto
dc.contributor.author Tassinari, Carlo Alberto
dc.contributor.author Riguzzi, Patrizia
dc.contributor.author Nobile, Carlo
dc.contributor.author Sanz, Pascual
dc.contributor.author Serratosa, José María
dc.contributor.author Gómez-Garré, Pilar
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.date.accessioned 2015-06-17T13:10:38Z
dc.date.available 2015-06-17T13:10:38Z
dc.date.issued 2011-07-05
dc.identifier.citation Plos One 6.6 (2011): e21294 en_US
dc.identifier.issn 1932-6203 (online) en_US
dc.identifier.uri http://hdl.handle.net/10486/666877
dc.description.abstract Lafora disease is an autosomal recessive form of progressive myoclonus epilepsy with no effective therapy. Although the outcome is always unfavorable, onset of symptoms and progression of the disease may vary. We aimed to identify modifier genes that may contribute to the clinical course of Lafora disease patients with EPM2A or EPM2B mutations. We established a list of 43 genes coding for proteins related to laforin/malin function and/or glycogen metabolism and tested common polymorphisms for possible associations with phenotypic differences using a collection of Lafora disease families. Genotype and haplotype analysis showed that PPP1R3C may be associated with a slow progression of the disease. The PPP1R3C gene encodes protein targeting to glycogen (PTG). Glycogen targeting subunits play a major role in recruiting type 1 protein phosphatase (PP1) to glycogen-enriched cell compartments and in increasing the specific activity of PP1 toward specific glycogenic substrates (glycogen synthase and glycogen phosphorylase). Here, we report a new mutation (c.746A>G, N249S) in the PPP1R3C gene that results in a decreased capacity to induce glycogen synthesis and a reduced interaction with glycogen phosphorylase and laforin, supporting a key role of this mutation in the glycogenic activity of PTG. This variant was found in one of two affected siblings of a Lafora disease family characterized by a remarkable mild course. Our findings suggest that variations in PTG may condition the course of Lafora disease and establish PTG as a potential target for pharmacogenetic and therapeutic approaches en_US
dc.description.sponsorship This work was supported by grants from the Fundación Mutua Madrileña to PGG and RG, the Spanish Ministry of Education and Science (SAF2008- 01907, SAF2007-61003) to PS and JMS and from the Generalitat Valenciana (Prometeo 2009/051) to PS en_US
dc.format.extent 9 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Public Library of Science en_US
dc.relation.ispartof Plos One en_US
dc.rights © 2011 Guerrero et al. es_ES
dc.subject.other Lafora Disease en_US
dc.subject.other Genotype en_US
dc.subject.other Phosphoprotein Phosphatases en_US
dc.subject.other Mutation en_US
dc.subject.other Haplotypes en_US
dc.title A PTG variant contributes to a milder phenotype in Lafora disease en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.identifier.doi 10.1371/journal.pone.0021294 es_ES
dc.identifier.publicationfirstpage e21294 es_ES
dc.identifier.publicationissue 6 es_ES
dc.identifier.publicationlastpage e21294 es_ES
dc.identifier.publicationvolume 6 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en

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