The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

Detalhes bibliográficos
Autor(a) principal: Ferreira, S.
Data de Publicação: 2015
Outros Autores: Ortiz, A., Germain, D.P., Viana-Baptista, M., Caldeira-Gomes, A., Camprecios, M., Fenollar-Cortés., M, Gallegos-Villalobos, Á., Garcia, D., García-Robles, J.A., Egido, J., Gutiérrez-Rivas, E., Herrero, J.A., Mas, S., Oancea, R., Péres, P., Salazar-Martín, L.M., Solera-Garcia, J., Alves, H., Garman, S.C., Oliveira, J.P.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/3338
Resumo: Acessível em: www.ncbi.nlm.nih.gov/pmc/articles/PMC4423738/
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spelling The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studiesFabry diseaseGLA geneR118CVariant p.(Arg118Cys)α-Galactosidase AAcessível em: www.ncbi.nlm.nih.gov/pmc/articles/PMC4423738/Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition.ElsevierRepositório Científico do Instituto Nacional de SaúdeFerreira, S.Ortiz, A.Germain, D.P.Viana-Baptista, M.Caldeira-Gomes, A.Camprecios, M.Fenollar-Cortés., MGallegos-Villalobos, Á.Garcia, D.García-Robles, J.A.Egido, J.Gutiérrez-Rivas, E.Herrero, J.A.Mas, S.Oancea, R.Péres, P.Salazar-Martín, L.M.Solera-Garcia, J.Alves, H.Garman, S.C.Oliveira, J.P.2016-02-16T15:59:04Z2015-022015-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/3338engMol Genet Metab. 2015 Feb;114(2):248-58. doi: 10.1016/j.ymgme.2014.11.004. Epub 2014 Nov 9.1096-719210.1016/j.ymgme.2014.11.004info: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:RCAAP2023-07-20T15:39:33Zoai:repositorio.insa.pt:10400.18/3338Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:37:56.681172Repositório 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 The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies
title The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies
spellingShingle The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies
Ferreira, S.
Fabry disease
GLA gene
R118C
Variant p.(Arg118Cys)
α-Galactosidase A
title_short The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies
title_full The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies
title_fullStr The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies
title_full_unstemmed The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies
title_sort The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies
author Ferreira, S.
author_facet Ferreira, S.
Ortiz, A.
Germain, D.P.
Viana-Baptista, M.
Caldeira-Gomes, A.
Camprecios, M.
Fenollar-Cortés., M
Gallegos-Villalobos, Á.
Garcia, D.
García-Robles, J.A.
Egido, J.
Gutiérrez-Rivas, E.
Herrero, J.A.
Mas, S.
Oancea, R.
Péres, P.
Salazar-Martín, L.M.
Solera-Garcia, J.
Alves, H.
Garman, S.C.
Oliveira, J.P.
author_role author
author2 Ortiz, A.
Germain, D.P.
Viana-Baptista, M.
Caldeira-Gomes, A.
Camprecios, M.
Fenollar-Cortés., M
Gallegos-Villalobos, Á.
Garcia, D.
García-Robles, J.A.
Egido, J.
Gutiérrez-Rivas, E.
Herrero, J.A.
Mas, S.
Oancea, R.
Péres, P.
Salazar-Martín, L.M.
Solera-Garcia, J.
Alves, H.
Garman, S.C.
Oliveira, J.P.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Ferreira, S.
Ortiz, A.
Germain, D.P.
Viana-Baptista, M.
Caldeira-Gomes, A.
Camprecios, M.
Fenollar-Cortés., M
Gallegos-Villalobos, Á.
Garcia, D.
García-Robles, J.A.
Egido, J.
Gutiérrez-Rivas, E.
Herrero, J.A.
Mas, S.
Oancea, R.
Péres, P.
Salazar-Martín, L.M.
Solera-Garcia, J.
Alves, H.
Garman, S.C.
Oliveira, J.P.
dc.subject.por.fl_str_mv Fabry disease
GLA gene
R118C
Variant p.(Arg118Cys)
α-Galactosidase A
topic Fabry disease
GLA gene
R118C
Variant p.(Arg118Cys)
α-Galactosidase A
description Acessível em: www.ncbi.nlm.nih.gov/pmc/articles/PMC4423738/
publishDate 2015
dc.date.none.fl_str_mv 2015-02
2015-02-01T00:00:00Z
2016-02-16T15:59:04Z
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/10400.18/3338
url http://hdl.handle.net/10400.18/3338
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Mol Genet Metab. 2015 Feb;114(2):248-58. doi: 10.1016/j.ymgme.2014.11.004. Epub 2014 Nov 9.
1096-7192
10.1016/j.ymgme.2014.11.004
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 Elsevier
publisher.none.fl_str_mv Elsevier
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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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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