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Mutation Spectrum in the CACNA1A Gene in 49 Patients with Episodic Ataxia

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dc.contributor.author Sintas, Cèlia
dc.contributor.author Carreño, Oriel
dc.contributor.author Fernández Castillo, Noelia
dc.contributor.author Corominas, Roser
dc.contributor.author Vila Pueyo, Marta
dc.contributor.author Toma, Claudio
dc.contributor.author Cuenca-León, Ester
dc.contributor.author Barroeta, Isabel
dc.contributor.author Roig, Carles
dc.contributor.author Volpini, Victor
dc.contributor.author Macaya, Alfons
dc.contributor.author Cormand, Bru
dc.date.accessioned 2018-07-27T07:32:59Z
dc.date.available 2018-07-27T07:32:59Z
dc.date.issued 2017
dc.identifier.citation Sintas C, Carreño O, Fernàndez-Castillo N, Corominas R, Vila-Pueyo M, Toma C. et al. Mutation Spectrum in the CACNA1A Gene in 49 Patients with Episodic Ataxia. Sci Rep. 2017 May 31;7(1):2514. DOI: 10.1038/s41598-017-02554-x
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10230/35306
dc.description.abstract Episodic ataxia is an autosomal dominant ion channel disorder characterized by episodes of imbalance and incoordination. The disease is genetically heterogeneous and is classified as episodic ataxia type 2 (EA2) when it is caused by a mutation in the CACNA1A gene, encoding the α1A subunit of the P/Q-type voltage-gated calcium channel Cav2.1. The vast majority of EA2 disease-causing variants are loss-of-function (LoF) point changes leading to decreased channel currents. CACNA1A exonic deletions have also been reported in EA2 using quantitative approaches. We performed a mutational screening of the CACNA1A gene, including the promoter and 3'UTR regions, in 49 unrelated patients diagnosed with episodic ataxia. When pathogenic variants were not found by sequencing, we performed a copy number variant (CNV) analysis to screen for duplications or deletions. Overall, sequencing screening allowed identification of six different point variants (three nonsense and three missense changes) and two coding indels, one of them found in two unrelated patients. Additionally, CNV analysis identified a deletion in a patient spanning exon 35 as a result of a recombination event between flanking intronic Alu sequences. This study allowed identification of potentially pathogenic alterations in our sample, five of them novel, which cover 20% of the patients (10/49). Our data suggest that most of these variants are disease-causing, although functional studies are required.
dc.description.sponsorship The funding for this study was provided by the Spanish Ministerio de Economía y Competitividad (SAF2009-13182-C01, SAF2009-13182-C03), AGAUR (2014SGR-0932, 2009SGR-0078) and Fundació La Marató de TV3 (grant 100731). These institutions had no further role in study design, collection, analysis, interpretation of data or in the submission of this paper for publication. CS and OC were supported by Ministerio de Economía y Competitividad (BES-2007-16450 and BES-2010-033895, respectively) and NF-C by Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER, ISCIII). MV-P was supported by a predoctoral grant from VHIR, Barcelona (Spain). CT was supported by the European Union (Marie Curie, PIEF-GA-2009-254930). EC-L is the recipient of the Beatriu de Pinós programme scholarship (BP-DGR 2010).
dc.format.mimetype application/pdf
dc.language.iso spa
dc.publisher Nature Publishing Group
dc.rights Copyright © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Atàxia
dc.subject.other Gens
dc.title Mutation Spectrum in the CACNA1A Gene in 49 Patients with Episodic Ataxia
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41598-017-02554-x
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/254930
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-13182-C01
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-13182-C03
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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