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

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 clinica...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/25626
Acceso en línea:http://hdl.handle.net/10230/25626
http://dx.doi.org/10.1002/mgg3.24
Access Level:acceso abierto
Palabra clave:Migranya -- Aspectes genètics
ATP1A2
CACNA1A
Functional studies
Hemiplegic migraine
Mutation analysis
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spelling Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studiesCarreño, OrielCorominas, RoserSerra Pascual, Selma A., 1981-Sintas, CèliaFernández Castillo, NoeliaVila Pueyo, MartaToma, ClaudioGené, GemmaPons, RoserLlaneza, MiguelSobrido, María JesúsGrinberg, DanielValverde, M. A. (Miguel Ángel), 1963-Fernández-Fernández, José Manuel, 1967-Macaya, AlfonsCormand, BruMigranya -- Aspectes genèticsATP1A2CACNA1AFunctional studiesHemiplegic migraineMutation analysisHemiplegic 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.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).Wiley201620162013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/25626http://dx.doi.org/10.1002/mgg3.24reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésMolecular genetics & genomic medicine. 2013;1(4):206-22info:eu-repo/grantAgreement/ES/3PN/SAF2012-31089info:eu-repo/grantAgreement/ES/3PN/SAF2012-3814info:eu-repo/grantAgreement/ES/3PN/BES2010-033895info:eu-repo/grantAgreement/ES/3PN/ SAF2009-13182info:eu-repo/grantAgreement/EC/FP7/254930© 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.http://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/256262026-06-12T07:21:37Z
dc.title.none.fl_str_mv Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies
title Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies
spellingShingle Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies
Carreño, Oriel
Migranya -- Aspectes genètics
ATP1A2
CACNA1A
Functional studies
Hemiplegic migraine
Mutation analysis
title_short Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies
title_full Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies
title_fullStr Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies
title_full_unstemmed Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies
title_sort Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies
dc.creator.none.fl_str_mv 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
author Carreño, Oriel
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Migranya -- Aspectes genètics
ATP1A2
CACNA1A
Functional studies
Hemiplegic migraine
Mutation analysis
topic Migranya -- Aspectes genètics
ATP1A2
CACNA1A
Functional studies
Hemiplegic migraine
Mutation analysis
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/25626
http://dx.doi.org/10.1002/mgg3.24
url http://hdl.handle.net/10230/25626
http://dx.doi.org/10.1002/mgg3.24
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Molecular genetics & genomic medicine. 2013;1(4):206-22
info:eu-repo/grantAgreement/ES/3PN/SAF2012-31089
info:eu-repo/grantAgreement/ES/3PN/SAF2012-3814
info:eu-repo/grantAgreement/ES/3PN/BES2010-033895
info:eu-repo/grantAgreement/ES/3PN/ SAF2009-13182
info:eu-repo/grantAgreement/EC/FP7/254930
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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