Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy
Background: Between 8% and 22% of female carriers of DMD mutations exhibit clinical symptoms of variable severity. Development of symptoms in DMD mutation carriers without chromosomal rearrangements has been attributed to skewed X-chromosome inactivation (XCI) favouring predominant expression of the...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2012 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositório: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglês |
| OAI Identifier: | oai:ddd.uab.cat:304924 |
| Acesso em linha: | https://ddd.uab.cat/record/304924 https://dx.doi.org/urn:doi:10.1186/1750-1172-7-82 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Becker muscular dystrophy DMD Duchenne muscular dystrophy Dystrophin Symptomatic carrier X-chromosome inactivation |
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Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathyJuan-Mateu, JonàsRodríguez, María JoséNascimento, AndrésJiménez-Mallebrera, CeciliaGonzález Quereda, Lidia|||0000-0003-0715-6414Rivas, EloyParadas, Carmen|||0000-0002-6917-2236Madruga, MarcosSánchez-Ayaso, PedroJou, Cristina|||0000-0002-2223-7880González Mera, LauraMunell Casadesus, Francina|||0000-0001-8580-2819Roig Quilis, Manuel|||0000-0001-8415-9972Rabasa, M.Hernández-Lain, AurelioDiaz-Manera, Jordi|||0000-0003-2941-7988Gallardo, Eduard|||0000-0002-3942-3436Pascual Calvet, JordiVerdura, Edgard|||0000-0003-3856-2060Colomer, JaumeBaiget Bastús, MontserratOlivé i Plana, Montserrat|||0000-0001-5727-0165Gallano, Pia|||0000-0001-8104-2197Becker muscular dystrophyDMDDuchenne muscular dystrophyDystrophinSymptomatic carrierX-chromosome inactivationBackground: Between 8% and 22% of female carriers of DMD mutations exhibit clinical symptoms of variable severity. Development of symptoms in DMD mutation carriers without chromosomal rearrangements has been attributed to skewed X-chromosome inactivation (XCI) favouring predominant expression of the DMD mutant allele. However the prognostic use of XCI analysis is controversial. We aimed to evaluate the correlation between X-chromosome inactivation and development of clinical symptoms in a series of symptomatic female carriers of dystrophinopathy. Methods. We reviewed the clinical, pathological and genetic features of twenty-four symptomatic carriers covering a wide spectrum of clinical phenotypes. DMD gene analysis was performed using MLPA and whole gene sequencing in blood DNA and muscle cDNA. Blood and muscle DNA was used for X-chromosome inactivation (XCI) analysis thought the AR methylation assay in symptomatic carriers and their female relatives, asymptomatic carriers as well as non-carrier females. Results: Symptomatic carriers exhibited 49.2% more skewed XCI profiles than asymptomatic carriers. The extent of XCI skewing in blood tended to increase in line with the severity of muscle symptoms. Skewed XCI patterns were found in at least one first-degree female relative in 78.6% of symptomatic carrier families. No mutations altering XCI in the XIST gene promoter were found. Conclusions: Skewed XCI is in many cases familial inherited. The extent of XCI skewing is related to phenotype severity. However, the assessment of XCI by means of the AR methylation assay has a poor prognostic value, probably because the methylation status of the AR gene in muscle may not reflect in all cases the methylation status of the DMD gene. © 2012 Juan-Mateu et al.; licensee BioMed Central Ltd.Universitat Autònoma de Barcelona 22012-01-0120122012-01-01Article de revisióhttp://purl.org/coar/resource_type/c_dcae04bcVoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/304924https://dx.doi.org/urn:doi:10.1186/1750-1172-7-82reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3049242026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy |
| title |
Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy |
| spellingShingle |
Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy Juan-Mateu, Jonàs Becker muscular dystrophy DMD Duchenne muscular dystrophy Dystrophin Symptomatic carrier X-chromosome inactivation |
| title_short |
Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy |
| title_full |
Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy |
| title_fullStr |
Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy |
| title_full_unstemmed |
Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy |
| title_sort |
Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy |
| dc.creator.none.fl_str_mv |
Juan-Mateu, Jonàs Rodríguez, María José Nascimento, Andrés Jiménez-Mallebrera, Cecilia González Quereda, Lidia|||0000-0003-0715-6414 Rivas, Eloy Paradas, Carmen|||0000-0002-6917-2236 Madruga, Marcos Sánchez-Ayaso, Pedro Jou, Cristina|||0000-0002-2223-7880 González Mera, Laura Munell Casadesus, Francina|||0000-0001-8580-2819 Roig Quilis, Manuel|||0000-0001-8415-9972 Rabasa, M. Hernández-Lain, Aurelio Diaz-Manera, Jordi|||0000-0003-2941-7988 Gallardo, Eduard|||0000-0002-3942-3436 Pascual Calvet, Jordi Verdura, Edgard|||0000-0003-3856-2060 Colomer, Jaume Baiget Bastús, Montserrat Olivé i Plana, Montserrat|||0000-0001-5727-0165 Gallano, Pia|||0000-0001-8104-2197 |
| author |
Juan-Mateu, Jonàs |
| author_facet |
Juan-Mateu, Jonàs Rodríguez, María José Nascimento, Andrés Jiménez-Mallebrera, Cecilia González Quereda, Lidia|||0000-0003-0715-6414 Rivas, Eloy Paradas, Carmen|||0000-0002-6917-2236 Madruga, Marcos Sánchez-Ayaso, Pedro Jou, Cristina|||0000-0002-2223-7880 González Mera, Laura Munell Casadesus, Francina|||0000-0001-8580-2819 Roig Quilis, Manuel|||0000-0001-8415-9972 Rabasa, M. Hernández-Lain, Aurelio Diaz-Manera, Jordi|||0000-0003-2941-7988 Gallardo, Eduard|||0000-0002-3942-3436 Pascual Calvet, Jordi Verdura, Edgard|||0000-0003-3856-2060 Colomer, Jaume Baiget Bastús, Montserrat Olivé i Plana, Montserrat|||0000-0001-5727-0165 Gallano, Pia|||0000-0001-8104-2197 |
| author_role |
author |
| author2 |
Rodríguez, María José Nascimento, Andrés Jiménez-Mallebrera, Cecilia González Quereda, Lidia|||0000-0003-0715-6414 Rivas, Eloy Paradas, Carmen|||0000-0002-6917-2236 Madruga, Marcos Sánchez-Ayaso, Pedro Jou, Cristina|||0000-0002-2223-7880 González Mera, Laura Munell Casadesus, Francina|||0000-0001-8580-2819 Roig Quilis, Manuel|||0000-0001-8415-9972 Rabasa, M. Hernández-Lain, Aurelio Diaz-Manera, Jordi|||0000-0003-2941-7988 Gallardo, Eduard|||0000-0002-3942-3436 Pascual Calvet, Jordi Verdura, Edgard|||0000-0003-3856-2060 Colomer, Jaume Baiget Bastús, Montserrat Olivé i Plana, Montserrat|||0000-0001-5727-0165 Gallano, Pia|||0000-0001-8104-2197 |
| author2_role |
author author 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 |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Becker muscular dystrophy DMD Duchenne muscular dystrophy Dystrophin Symptomatic carrier X-chromosome inactivation |
| topic |
Becker muscular dystrophy DMD Duchenne muscular dystrophy Dystrophin Symptomatic carrier X-chromosome inactivation |
| description |
Background: Between 8% and 22% of female carriers of DMD mutations exhibit clinical symptoms of variable severity. Development of symptoms in DMD mutation carriers without chromosomal rearrangements has been attributed to skewed X-chromosome inactivation (XCI) favouring predominant expression of the DMD mutant allele. However the prognostic use of XCI analysis is controversial. We aimed to evaluate the correlation between X-chromosome inactivation and development of clinical symptoms in a series of symptomatic female carriers of dystrophinopathy. Methods. We reviewed the clinical, pathological and genetic features of twenty-four symptomatic carriers covering a wide spectrum of clinical phenotypes. DMD gene analysis was performed using MLPA and whole gene sequencing in blood DNA and muscle cDNA. Blood and muscle DNA was used for X-chromosome inactivation (XCI) analysis thought the AR methylation assay in symptomatic carriers and their female relatives, asymptomatic carriers as well as non-carrier females. Results: Symptomatic carriers exhibited 49.2% more skewed XCI profiles than asymptomatic carriers. The extent of XCI skewing in blood tended to increase in line with the severity of muscle symptoms. Skewed XCI patterns were found in at least one first-degree female relative in 78.6% of symptomatic carrier families. No mutations altering XCI in the XIST gene promoter were found. Conclusions: Skewed XCI is in many cases familial inherited. The extent of XCI skewing is related to phenotype severity. However, the assessment of XCI by means of the AR methylation assay has a poor prognostic value, probably because the methylation status of the AR gene in muscle may not reflect in all cases the methylation status of the DMD gene. © 2012 Juan-Mateu et al.; licensee BioMed Central Ltd. |
| publishDate |
2012 |
| dc.date.none.fl_str_mv |
2 2012-01-01 2012 2012-01-01 |
| dc.type.none.fl_str_mv |
Article de revisió http://purl.org/coar/resource_type/c_dcae04bc VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
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https://ddd.uab.cat/record/304924 https://dx.doi.org/urn:doi:10.1186/1750-1172-7-82 |
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https://ddd.uab.cat/record/304924 https://dx.doi.org/urn:doi:10.1186/1750-1172-7-82 |
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Inglés eng |
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Inglés |
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eng |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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