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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/1801
Acceder
id CONICETDig_bf358234acbdc959e8d6d05862ab9ff4
oai_identifier_str oai:ri.conicet.gov.ar:11336/1801
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-09-29T09:54:02Zoai: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:34982025-09-29 09:54:02.443CONICET 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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score 13.070432

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