Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family
Autor(a) principal: | |
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Data de Publicação: | 2003 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/349 |
Resumo: | Background: Different mutations in the 1A-subunit of the brain P/Q-type calcium channel gene (CACNA1A) are responsible for familial hemiplegic migraine (FHM), episodic ataxia type 2, and spinocerebellar ataxia type 6 (SCA6). Missense and splice site mutations have been found in FHM and episodic ataxia type 2, respectively, whereas a CAG repeat in the CACNA1A gene was found expanded in patients with SCA6. Objective: To identify the disease causing mutation in a large family of patients with phenotypes of hemiplegic migraine with or without cerebellar signs or permanent cerebellar ataxia without migraine inherited in a dominant manner. Patients and Methods: We examined 15 patients from a large family identified through a systematic survey of hereditary ataxias being conducted in Portugal. Linkage analysis was performed with CACNA1A gene markers, and mutation analysis was performed by single strand conformational polymorphism analysis and sequencing. Results: Genetic linkage analysis with CACNA1A intragenic markers showed positive LOD scores. The maximal LOD score was obtained with the polymorphic CAG repeat (Zmax=4.47, =0). By single-strand conformational polymorphism analysis, a shift in exon 13 of the CACNA1A gene was detected in all patients.AG-to-A substitution was then identified, resulting in an arginine-to-glutamine change at codon 583 of this calcium channel 1A-subunit. Conclusions: The disease-causing mutation in this family was identified, showing that a unique mutation in the CACNA1A gene causes several phenotypes, including those of SCA6 and FHM, thus suggesting that SCA6 and FHM are not only allelic diseases but are the same disorder with a large phenotypic variability. |
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Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large familyBackground: Different mutations in the 1A-subunit of the brain P/Q-type calcium channel gene (CACNA1A) are responsible for familial hemiplegic migraine (FHM), episodic ataxia type 2, and spinocerebellar ataxia type 6 (SCA6). Missense and splice site mutations have been found in FHM and episodic ataxia type 2, respectively, whereas a CAG repeat in the CACNA1A gene was found expanded in patients with SCA6. Objective: To identify the disease causing mutation in a large family of patients with phenotypes of hemiplegic migraine with or without cerebellar signs or permanent cerebellar ataxia without migraine inherited in a dominant manner. Patients and Methods: We examined 15 patients from a large family identified through a systematic survey of hereditary ataxias being conducted in Portugal. Linkage analysis was performed with CACNA1A gene markers, and mutation analysis was performed by single strand conformational polymorphism analysis and sequencing. Results: Genetic linkage analysis with CACNA1A intragenic markers showed positive LOD scores. The maximal LOD score was obtained with the polymorphic CAG repeat (Zmax=4.47, =0). By single-strand conformational polymorphism analysis, a shift in exon 13 of the CACNA1A gene was detected in all patients.AG-to-A substitution was then identified, resulting in an arginine-to-glutamine change at codon 583 of this calcium channel 1A-subunit. Conclusions: The disease-causing mutation in this family was identified, showing that a unique mutation in the CACNA1A gene causes several phenotypes, including those of SCA6 and FHM, thus suggesting that SCA6 and FHM are not only allelic diseases but are the same disorder with a large phenotypic variability.Fundação para a Ciência e TecnologiaAmerican Medical AssociationRepositório Científico do Centro Hospitalar Universitário de Santo AntónioAlonso, I.Barros, J.Tuna, A.Coelho, J.Sequeira, J.Silveira, I.Coutinho, P.2010-07-31T06:00:00Z2003-042003-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/349engArch Neurol. 2003 Apr;60(4):610-4.0003-9942info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T10:51:59Zoai:repositorio.chporto.pt:10400.16/349Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:36:23.404851Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family |
title |
Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family |
spellingShingle |
Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family Alonso, I. |
title_short |
Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family |
title_full |
Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family |
title_fullStr |
Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family |
title_full_unstemmed |
Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family |
title_sort |
Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine caused by a unique CACNA1A missense mutation in patients from a large family |
author |
Alonso, I. |
author_facet |
Alonso, I. Barros, J. Tuna, A. Coelho, J. Sequeira, J. Silveira, I. Coutinho, P. |
author_role |
author |
author2 |
Barros, J. Tuna, A. Coelho, J. Sequeira, J. Silveira, I. Coutinho, P. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
dc.contributor.author.fl_str_mv |
Alonso, I. Barros, J. Tuna, A. Coelho, J. Sequeira, J. Silveira, I. Coutinho, P. |
description |
Background: Different mutations in the 1A-subunit of the brain P/Q-type calcium channel gene (CACNA1A) are responsible for familial hemiplegic migraine (FHM), episodic ataxia type 2, and spinocerebellar ataxia type 6 (SCA6). Missense and splice site mutations have been found in FHM and episodic ataxia type 2, respectively, whereas a CAG repeat in the CACNA1A gene was found expanded in patients with SCA6. Objective: To identify the disease causing mutation in a large family of patients with phenotypes of hemiplegic migraine with or without cerebellar signs or permanent cerebellar ataxia without migraine inherited in a dominant manner. Patients and Methods: We examined 15 patients from a large family identified through a systematic survey of hereditary ataxias being conducted in Portugal. Linkage analysis was performed with CACNA1A gene markers, and mutation analysis was performed by single strand conformational polymorphism analysis and sequencing. Results: Genetic linkage analysis with CACNA1A intragenic markers showed positive LOD scores. The maximal LOD score was obtained with the polymorphic CAG repeat (Zmax=4.47, =0). By single-strand conformational polymorphism analysis, a shift in exon 13 of the CACNA1A gene was detected in all patients.AG-to-A substitution was then identified, resulting in an arginine-to-glutamine change at codon 583 of this calcium channel 1A-subunit. Conclusions: The disease-causing mutation in this family was identified, showing that a unique mutation in the CACNA1A gene causes several phenotypes, including those of SCA6 and FHM, thus suggesting that SCA6 and FHM are not only allelic diseases but are the same disorder with a large phenotypic variability. |
publishDate |
2003 |
dc.date.none.fl_str_mv |
2003-04 2003-04-01T00:00:00Z 2010-07-31T06:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.16/349 |
url |
http://hdl.handle.net/10400.16/349 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Arch Neurol. 2003 Apr;60(4):610-4. 0003-9942 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
American Medical Association |
publisher.none.fl_str_mv |
American Medical Association |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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