Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization
- Autores
- Giliberto, Florencia; Radic, Claudia Pamela; Luce, Leonela; Ferreiro, Verónica; de Brasi, Carlos Daniel; Szijan, Irena
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by mutations in the dystrophin gene and is characterized by muscle degeneration and death. DMD affects males; females being asymptomatic carriers of mutations. However, some of them manifest symptoms due to a translocation between X chromosome and an autosome or to a heterozygous mutation leading to inactivation of most of their normal X chromosome. Six symptomatic female carriers and two asymptomatic were analyzed by: I) Segregation of STRs-(CA)n and MLPA assays to detect a hemizygous alteration, and II) X chromosome inactivation pattern to uncover the reason for symptoms in these females. The symptomatic females shared mild but progressive muscular weakness and increased serum creatin kinase (CK) levels. Levels of dystrophin protein were below normal or absent in many fibers. Segregation of STRs-(CA)n revealed hemizygous patterns in three patients, which were confirmed by MLPA. In addition, this analysis showed a duplication in another patient. X chromosome inactivation assay revealed a skewed X inactivation pattern in the symptomatic females and a random inactivation pattern in the asymptomatic ones. Our results support the hypothesis that the DMD phenotype in female carriers of a dystrophin mutation has a direct correlation with a skewed X-chromosome inactivation pattern.
Fil: Giliberto, Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Fil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Luce, Leonela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Fil: Ferreiro, Verónica. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Instituto de Neurociencias Aplicadas; Argentina. Laboratorio de Genética Molecular Diagnóstica; Argentina
Fil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina - Materia
-
Duchenne Muscular Dystrophy,
Symptomatic Female Carriers
Clinical Symptoms
Haplotypes
Mutations Mutations
Skewed X Inactivation - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/1801
Ver los metadatos del registro completo
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Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterizationGiliberto, FlorenciaRadic, Claudia PamelaLuce, LeonelaFerreiro, Verónicade Brasi, Carlos DanielSzijan, IrenaDuchenne Muscular Dystrophy,Symptomatic Female CarriersClinical SymptomsHaplotypesMutations MutationsSkewed X Inactivationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by mutations in the dystrophin gene and is characterized by muscle degeneration and death. DMD affects males; females being asymptomatic carriers of mutations. However, some of them manifest symptoms due to a translocation between X chromosome and an autosome or to a heterozygous mutation leading to inactivation of most of their normal X chromosome. Six symptomatic female carriers and two asymptomatic were analyzed by: I) Segregation of STRs-(CA)n and MLPA assays to detect a hemizygous alteration, and II) X chromosome inactivation pattern to uncover the reason for symptoms in these females. The symptomatic females shared mild but progressive muscular weakness and increased serum creatin kinase (CK) levels. Levels of dystrophin protein were below normal or absent in many fibers. Segregation of STRs-(CA)n revealed hemizygous patterns in three patients, which were confirmed by MLPA. In addition, this analysis showed a duplication in another patient. X chromosome inactivation assay revealed a skewed X inactivation pattern in the symptomatic females and a random inactivation pattern in the asymptomatic ones. Our results support the hypothesis that the DMD phenotype in female carriers of a dystrophin mutation has a direct correlation with a skewed X-chromosome inactivation pattern.Fil: Giliberto, Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; ArgentinaFil: Luce, Leonela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Ferreiro, Verónica. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Instituto de Neurociencias Aplicadas; Argentina. Laboratorio de Genética Molecular Diagnóstica; ArgentinaFil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; ArgentinaFil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaElsevier2014-01-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1801Giliberto, Florencia; Radic, Claudia Pamela; Luce, Leonela; Ferreiro, Verónica; de Brasi, Carlos Daniel; et al.; Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization; Elsevier; Journal of the Neurological Sciences; 336; 1-2; 15-1-2014; 36-410022-510Xenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jns.2013.09.036info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:55Zoai:ri.conicet.gov.ar:11336/1801instacron: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:34982025-09-03 09:53:55.461CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization |
title |
Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization |
spellingShingle |
Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization Giliberto, Florencia Duchenne Muscular Dystrophy, Symptomatic Female Carriers Clinical Symptoms Haplotypes Mutations Mutations Skewed X Inactivation |
title_short |
Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization |
title_full |
Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization |
title_fullStr |
Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization |
title_full_unstemmed |
Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization |
title_sort |
Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization |
dc.creator.none.fl_str_mv |
Giliberto, Florencia Radic, Claudia Pamela Luce, Leonela Ferreiro, Verónica de Brasi, Carlos Daniel Szijan, Irena |
author |
Giliberto, Florencia |
author_facet |
Giliberto, Florencia Radic, Claudia Pamela Luce, Leonela Ferreiro, Verónica de Brasi, Carlos Daniel Szijan, Irena |
author_role |
author |
author2 |
Radic, Claudia Pamela Luce, Leonela Ferreiro, Verónica de Brasi, Carlos Daniel Szijan, Irena |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
Duchenne Muscular Dystrophy, Symptomatic Female Carriers Clinical Symptoms Haplotypes Mutations Mutations Skewed X Inactivation |
topic |
Duchenne Muscular Dystrophy, Symptomatic Female Carriers Clinical Symptoms Haplotypes Mutations Mutations Skewed X Inactivation |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by mutations in the dystrophin gene and is characterized by muscle degeneration and death. DMD affects males; females being asymptomatic carriers of mutations. However, some of them manifest symptoms due to a translocation between X chromosome and an autosome or to a heterozygous mutation leading to inactivation of most of their normal X chromosome. Six symptomatic female carriers and two asymptomatic were analyzed by: I) Segregation of STRs-(CA)n and MLPA assays to detect a hemizygous alteration, and II) X chromosome inactivation pattern to uncover the reason for symptoms in these females. The symptomatic females shared mild but progressive muscular weakness and increased serum creatin kinase (CK) levels. Levels of dystrophin protein were below normal or absent in many fibers. Segregation of STRs-(CA)n revealed hemizygous patterns in three patients, which were confirmed by MLPA. In addition, this analysis showed a duplication in another patient. X chromosome inactivation assay revealed a skewed X inactivation pattern in the symptomatic females and a random inactivation pattern in the asymptomatic ones. Our results support the hypothesis that the DMD phenotype in female carriers of a dystrophin mutation has a direct correlation with a skewed X-chromosome inactivation pattern. Fil: Giliberto, Florencia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina Fil: Luce, Leonela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina Fil: Ferreiro, Verónica. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Instituto de Neurociencias Aplicadas; Argentina. Laboratorio de Genética Molecular Diagnóstica; Argentina Fil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina Fil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina |
description |
Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by mutations in the dystrophin gene and is characterized by muscle degeneration and death. DMD affects males; females being asymptomatic carriers of mutations. However, some of them manifest symptoms due to a translocation between X chromosome and an autosome or to a heterozygous mutation leading to inactivation of most of their normal X chromosome. Six symptomatic female carriers and two asymptomatic were analyzed by: I) Segregation of STRs-(CA)n and MLPA assays to detect a hemizygous alteration, and II) X chromosome inactivation pattern to uncover the reason for symptoms in these females. The symptomatic females shared mild but progressive muscular weakness and increased serum creatin kinase (CK) levels. Levels of dystrophin protein were below normal or absent in many fibers. Segregation of STRs-(CA)n revealed hemizygous patterns in three patients, which were confirmed by MLPA. In addition, this analysis showed a duplication in another patient. X chromosome inactivation assay revealed a skewed X inactivation pattern in the symptomatic females and a random inactivation pattern in the asymptomatic ones. Our results support the hypothesis that the DMD phenotype in female carriers of a dystrophin mutation has a direct correlation with a skewed X-chromosome inactivation pattern. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-01-15 |
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/11336/1801 Giliberto, Florencia; Radic, Claudia Pamela; Luce, Leonela; Ferreiro, Verónica; de Brasi, Carlos Daniel; et al.; Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization; Elsevier; Journal of the Neurological Sciences; 336; 1-2; 15-1-2014; 36-41 0022-510X |
url |
http://hdl.handle.net/11336/1801 |
identifier_str_mv |
Giliberto, Florencia; Radic, Claudia Pamela; Luce, Leonela; Ferreiro, Verónica; de Brasi, Carlos Daniel; et al.; Symptomatic female carriers of Duchenne Muscular Dystrophy (DMD): genetic and clinical characterization; Elsevier; Journal of the Neurological Sciences; 336; 1-2; 15-1-2014; 36-41 0022-510X |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jns.2013.09.036 |
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 |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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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1842269256800010240 |
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13.13397 |