X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients

Autores
Amorosi, Cyntia Anabel; Myskóva, Helena; Monti, Mariela Roxana; Argaraña, Carlos Enrique; Morita, Masashi; Kemp, Stephan; Dodelson de Kremer, Raquel; Dvoráková, Lenka; Oller de Ramírez, Ana María
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
X-linked adrenoleukodystrophy (X-ALD) is an inherited disease associated with mutations in ABCD1 gene, located on Xq28. It is characterized by increased concentration of very long chain fatty acids (VLCFAs) in plasma and in adrenal, testicular and nervous tissues, due to a failure in peroxisomal -oxidation. Clinical heterogeneity varies from presymptomatic individuals to rapidly progressive cerebral ALD forms. A total of 44 individuals from 10 unrelated X-ALD Argentinean pedigrees were involved in this study. We examined the ABCD1 gene in 28 patients including carriers by sequencing of genomic PCR products. In 10 families there were 9 different mutations, eight of which were novel. The new changes found were verified by a combination of methods: bioinformatics programs and functional analysis. The spectrum of mutations consists of 3 frameshift, an insertion (p.Arg285fs*16), a deletion (p.Thr254Argfs*82) and a duplication (p.Glu380Argfs*21); a deletion (p.Ser572_Asp575del), a splicing mutation (c.1081+5G>C) and 3 novel single base pair substitution (p.Ala341Asp, p.His420Pro and p.Tyr547Cys). In one patient 2 changes were found: 1 known (c.2006A>G, p.His669Arg) and 1 new (c.55G>T, p.Ala19Ser). Expression studies of last change suggested that is a polymorphism because plasmid encoding ALDP with this change was effective in the restoration of defective -oxidation in X-ALD fibroblasts. But without sufficient evidence for c.55G>T (p.Ala19Ser), therefore we call variation change. In total four polymorphisms were found by the sequencing of the ABCD1 gene from our patients: two novel intronic IVS6+14T>A, IVS9-32C>T both frequent in our patients and two known, c.1548G>A (p.Leu516Leu) in exon 6 and c.2019C>T (p.Phe673Phe) in exon 10.
Fil: Amorosi, Cyntia Anabel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Myskóva, Helena. No especifíca;
Fil: Monti, Mariela Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Argaraña, Carlos Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Morita, Masashi. University of Toyama; Japón
Fil: Kemp, Stephan. No especifíca;
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Dvoráková, Lenka. No especifíca;
Fil: Oller de Ramírez, Ana María. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Materia
X-LINKED ADRENOLEUKODYSTROPHY
ABCD1 GENE
ARGENTINEAN PATIENTS
ALDP
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/229668
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/229668
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean PatientsAmorosi, Cyntia AnabelMyskóva, HelenaMonti, Mariela RoxanaArgaraña, Carlos EnriqueMorita, MasashiKemp, StephanDodelson de Kremer, RaquelDvoráková, LenkaOller de Ramírez, Ana MaríaX-LINKED ADRENOLEUKODYSTROPHYABCD1 GENEARGENTINEAN PATIENTSALDPhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3X-linked adrenoleukodystrophy (X-ALD) is an inherited disease associated with mutations in ABCD1 gene, located on Xq28. It is characterized by increased concentration of very long chain fatty acids (VLCFAs) in plasma and in adrenal, testicular and nervous tissues, due to a failure in peroxisomal -oxidation. Clinical heterogeneity varies from presymptomatic individuals to rapidly progressive cerebral ALD forms. A total of 44 individuals from 10 unrelated X-ALD Argentinean pedigrees were involved in this study. We examined the ABCD1 gene in 28 patients including carriers by sequencing of genomic PCR products. In 10 families there were 9 different mutations, eight of which were novel. The new changes found were verified by a combination of methods: bioinformatics programs and functional analysis. The spectrum of mutations consists of 3 frameshift, an insertion (p.Arg285fs*16), a deletion (p.Thr254Argfs*82) and a duplication (p.Glu380Argfs*21); a deletion (p.Ser572_Asp575del), a splicing mutation (c.1081+5G>C) and 3 novel single base pair substitution (p.Ala341Asp, p.His420Pro and p.Tyr547Cys). In one patient 2 changes were found: 1 known (c.2006A>G, p.His669Arg) and 1 new (c.55G>T, p.Ala19Ser). Expression studies of last change suggested that is a polymorphism because plasmid encoding ALDP with this change was effective in the restoration of defective -oxidation in X-ALD fibroblasts. But without sufficient evidence for c.55G>T (p.Ala19Ser), therefore we call variation change. In total four polymorphisms were found by the sequencing of the ABCD1 gene from our patients: two novel intronic IVS6+14T>A, IVS9-32C>T both frequent in our patients and two known, c.1548G>A (p.Leu516Leu) in exon 6 and c.2019C>T (p.Phe673Phe) in exon 10.Fil: Amorosi, Cyntia Anabel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Myskóva, Helena. No especifíca;Fil: Monti, Mariela Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Argaraña, Carlos Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Morita, Masashi. University of Toyama; JapónFil: Kemp, Stephan. No especifíca;Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; ArgentinaFil: Dvoráková, Lenka. No especifíca;Fil: Oller de Ramírez, Ana María. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; ArgentinaPublic Library of Science2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/229668Amorosi, Cyntia Anabel; Myskóva, Helena; Monti, Mariela Roxana; Argaraña, Carlos Enrique; Morita, Masashi; et al.; X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients; Public Library of Science; Plos One; 7; 12; 10-2012; 1-81932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0052635info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0052635info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:33:55Zoai:ri.conicet.gov.ar:11336/229668instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:33:55.928CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients
title X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients
spellingShingle X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients
Amorosi, Cyntia Anabel
X-LINKED ADRENOLEUKODYSTROPHY
ABCD1 GENE
ARGENTINEAN PATIENTS
ALDP
title_short X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients
title_full X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients
title_fullStr X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients
title_full_unstemmed X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients
title_sort X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients
dc.creator.none.fl_str_mv Amorosi, Cyntia Anabel
Myskóva, Helena
Monti, Mariela Roxana
Argaraña, Carlos Enrique
Morita, Masashi
Kemp, Stephan
Dodelson de Kremer, Raquel
Dvoráková, Lenka
Oller de Ramírez, Ana María
author Amorosi, Cyntia Anabel
author_facet Amorosi, Cyntia Anabel
Myskóva, Helena
Monti, Mariela Roxana
Argaraña, Carlos Enrique
Morita, Masashi
Kemp, Stephan
Dodelson de Kremer, Raquel
Dvoráková, Lenka
Oller de Ramírez, Ana María
author_role author
author2 Myskóva, Helena
Monti, Mariela Roxana
Argaraña, Carlos Enrique
Morita, Masashi
Kemp, Stephan
Dodelson de Kremer, Raquel
Dvoráková, Lenka
Oller de Ramírez, Ana María
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv X-LINKED ADRENOLEUKODYSTROPHY
ABCD1 GENE
ARGENTINEAN PATIENTS
ALDP
topic X-LINKED ADRENOLEUKODYSTROPHY
ABCD1 GENE
ARGENTINEAN PATIENTS
ALDP
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv X-linked adrenoleukodystrophy (X-ALD) is an inherited disease associated with mutations in ABCD1 gene, located on Xq28. It is characterized by increased concentration of very long chain fatty acids (VLCFAs) in plasma and in adrenal, testicular and nervous tissues, due to a failure in peroxisomal -oxidation. Clinical heterogeneity varies from presymptomatic individuals to rapidly progressive cerebral ALD forms. A total of 44 individuals from 10 unrelated X-ALD Argentinean pedigrees were involved in this study. We examined the ABCD1 gene in 28 patients including carriers by sequencing of genomic PCR products. In 10 families there were 9 different mutations, eight of which were novel. The new changes found were verified by a combination of methods: bioinformatics programs and functional analysis. The spectrum of mutations consists of 3 frameshift, an insertion (p.Arg285fs*16), a deletion (p.Thr254Argfs*82) and a duplication (p.Glu380Argfs*21); a deletion (p.Ser572_Asp575del), a splicing mutation (c.1081+5G>C) and 3 novel single base pair substitution (p.Ala341Asp, p.His420Pro and p.Tyr547Cys). In one patient 2 changes were found: 1 known (c.2006A>G, p.His669Arg) and 1 new (c.55G>T, p.Ala19Ser). Expression studies of last change suggested that is a polymorphism because plasmid encoding ALDP with this change was effective in the restoration of defective -oxidation in X-ALD fibroblasts. But without sufficient evidence for c.55G>T (p.Ala19Ser), therefore we call variation change. In total four polymorphisms were found by the sequencing of the ABCD1 gene from our patients: two novel intronic IVS6+14T>A, IVS9-32C>T both frequent in our patients and two known, c.1548G>A (p.Leu516Leu) in exon 6 and c.2019C>T (p.Phe673Phe) in exon 10.
Fil: Amorosi, Cyntia Anabel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Myskóva, Helena. No especifíca;
Fil: Monti, Mariela Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Argaraña, Carlos Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Morita, Masashi. University of Toyama; Japón
Fil: Kemp, Stephan. No especifíca;
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Dvoráková, Lenka. No especifíca;
Fil: Oller de Ramírez, Ana María. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
description X-linked adrenoleukodystrophy (X-ALD) is an inherited disease associated with mutations in ABCD1 gene, located on Xq28. It is characterized by increased concentration of very long chain fatty acids (VLCFAs) in plasma and in adrenal, testicular and nervous tissues, due to a failure in peroxisomal -oxidation. Clinical heterogeneity varies from presymptomatic individuals to rapidly progressive cerebral ALD forms. A total of 44 individuals from 10 unrelated X-ALD Argentinean pedigrees were involved in this study. We examined the ABCD1 gene in 28 patients including carriers by sequencing of genomic PCR products. In 10 families there were 9 different mutations, eight of which were novel. The new changes found were verified by a combination of methods: bioinformatics programs and functional analysis. The spectrum of mutations consists of 3 frameshift, an insertion (p.Arg285fs*16), a deletion (p.Thr254Argfs*82) and a duplication (p.Glu380Argfs*21); a deletion (p.Ser572_Asp575del), a splicing mutation (c.1081+5G>C) and 3 novel single base pair substitution (p.Ala341Asp, p.His420Pro and p.Tyr547Cys). In one patient 2 changes were found: 1 known (c.2006A>G, p.His669Arg) and 1 new (c.55G>T, p.Ala19Ser). Expression studies of last change suggested that is a polymorphism because plasmid encoding ALDP with this change was effective in the restoration of defective -oxidation in X-ALD fibroblasts. But without sufficient evidence for c.55G>T (p.Ala19Ser), therefore we call variation change. In total four polymorphisms were found by the sequencing of the ABCD1 gene from our patients: two novel intronic IVS6+14T>A, IVS9-32C>T both frequent in our patients and two known, c.1548G>A (p.Leu516Leu) in exon 6 and c.2019C>T (p.Phe673Phe) in exon 10.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/229668
Amorosi, Cyntia Anabel; Myskóva, Helena; Monti, Mariela Roxana; Argaraña, Carlos Enrique; Morita, Masashi; et al.; X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients; Public Library of Science; Plos One; 7; 12; 10-2012; 1-8
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/229668
identifier_str_mv Amorosi, Cyntia Anabel; Myskóva, Helena; Monti, Mariela Roxana; Argaraña, Carlos Enrique; Morita, Masashi; et al.; X-Linked Adrenoleukodystrophy: Molecular and Functional Analysis of the ABCD1 Gene in Argentinean Patients; Public Library of Science; Plos One; 7; 12; 10-2012; 1-8
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0052635
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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