Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies

Carreño, Oriel; Corominas, Roser; Serra Pascual, Selma A., 1981-; Sintas, Cèlia; Fernández Castillo, Noelia; Vila Pueyo, Marta; Toma, Claudio; Gené, Gemma; Pons, Roser; Llaneza, Miguel; Sobrido, María Jesús; Grinberg, Daniel; Valverde, M. A. (Miguel Ángel), 1963-; Fernández-Fernández, José Manuel, 1967-; Macaya, Alfons; Cormand, Bru

Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies

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dc.contributor.author Carreño, Orielca
dc.contributor.author Corominas, Roserca
dc.contributor.author Serra Pascual, Selma A., 1981-ca
dc.contributor.author Sintas, Cèliaca
dc.contributor.author Fernández Castillo, Noeliaca
dc.contributor.author Vila Pueyo, Martaca
dc.contributor.author Toma, Claudioca
dc.contributor.author Gené, Gemmaca
dc.contributor.author Pons, Roserca
dc.contributor.author Llaneza, Miguelca
dc.contributor.author Sobrido, María Jesúsca
dc.contributor.author Grinberg, Danielca
dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-ca
dc.contributor.author Fernández-Fernández, José Manuel, 1967-ca
dc.contributor.author Macaya, Alfonsca
dc.contributor.author Cormand, Bruca
dc.date.accessioned 2016-01-21T14:01:51Z
dc.date.available 2016-01-21T14:01:51Z
dc.date.issued 2013
dc.description.abstract Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in four genes (CACNA1A, ATP1A2, SCN1A and PRRT2) have been detected in familial and in sporadic cases. This genetically and clinically heterogeneous disorder is often accompanied by permanent ataxia, epileptic seizures, mental retardation, and chronic progressive cerebellar atrophy. Here we report a mutation screening in the CACNA1A and ATP1A2 genes in 18 patients with HM. Furthermore, intragenic copy number variant (CNV) analysis was performed in CACNA1A using quantitative approaches. We identified four previously described missense CACNA1A mutations (p.Ser218Leu, p.Thr501Met, p.Arg583Gln, and p.Thr666Met) and two missense changes in the ATP1A2 gene, the previously described p.Ala606Thr and the novel variant p.Glu825Lys. No structural variants were found. This genetic screening allowed the identification of more than 30% of the disease alleles, all present in a heterozygous state. Functional consequences of the CACNA1A-p.Thr501Met mutation, previously described only in association with episodic ataxia, and ATP1A2-p.Glu825Lys, were investigated by means of electrophysiological studies, cell viability assays or Western blot analysis. Our data suggest that both these variants are disease-causing.ca
dc.description.sponsorship The work was funded by the Spanish Ministry of Science and Innovation, the Spanish Ministry of Economy and Competitiveness,Fondos Europeos de Desarrollo Regional (FEDER) and Plan E (Grants SAF2012 -31089, SAF2012-3814 0, BES-2010-033895, SAF2009-13182-C03-01, SAF2009-13182-C03-02, and SAF2009-13182-C03-03), Fondo de Investigación Sanitaria (Cardiovascular Disease Network RD12/0042/0014) and Generalitat de Catalunya (grants 2009SGR0971, 2009SGR0078 and 2009SGR1369). M. A. V. and N. F.-C. are the recipients of an ICREA Academia Award (Generalitat de Catalunya) and a grant from “CIBER-ER,” respectively. C. T. was supported by the European Union (Marie Curie, PIEF-GA-2009-254930).
dc.format.mimetype application/pdfca
dc.identifier.citation Carreño O, Corominas R, Serra SA, Sintas C, Fernández-Castillo N, Vila-Pueyo M et al. Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies. Molecular genetics & genomic medicine. 2013;1(4):206-22. DOI: 10.1002/mgg3.24ca
dc.identifier.doi http://dx.doi.org/10.1002/mgg3.24
dc.identifier.issn 2324-9269
dc.identifier.uri http://hdl.handle.net/10230/25626
dc.language.iso engca
dc.publisher Wileyca
dc.relation.ispartof Molecular genetics & genomic medicine. 2013;1(4):206-22
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-31089
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-3814
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BES2010-033895
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/ SAF2009-13182
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/254930
dc.rights © 2013 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/3.0/ca
dc.subject.keyword ATP1A2
dc.subject.keyword CACNA1A
dc.subject.keyword Functional studies
dc.subject.keyword Hemiplegic migraine
dc.subject.keyword Mutation analysis
dc.subject.other Migranya -- Aspectes genèticsca
dc.title Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studiesca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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