Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/51352 |
Resumo: | Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome -46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated by the inversion. However, and in spite of a balanced pattern of X inactivation, this patient displayed hypomethylation and an overexpression of the MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55 +/- 038) in comparison to a group of control individuals; the expression of the CDKL5 gene was similar to that of controls (mean fold change: 0.98 +/- 0.10). No gains or losses were detected in the breakpoint regions encompassing known or suspected transcription regulatory elements. We propose that the de-regulation of MECP2 expression in this patient may be due to alterations in long-range genomic interactions caused by the inversion and hypothesize that this type of epigenetic de-regulation of the MECP2 may be present in other RTT-like patients. |
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Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 geneEpigeneticsEpilepsyIntellectual disabilityNeurodevelopmentCiências Médicas::Medicina BásicaScience & TechnologyRett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome -46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated by the inversion. However, and in spite of a balanced pattern of X inactivation, this patient displayed hypomethylation and an overexpression of the MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55 +/- 038) in comparison to a group of control individuals; the expression of the CDKL5 gene was similar to that of controls (mean fold change: 0.98 +/- 0.10). No gains or losses were detected in the breakpoint regions encompassing known or suspected transcription regulatory elements. We propose that the de-regulation of MECP2 expression in this patient may be due to alterations in long-range genomic interactions caused by the inversion and hypothesize that this type of epigenetic de-regulation of the MECP2 may be present in other RTT-like patients.info:eu-repo/semantics/publishedVersionElsevierUniversidade do MinhoVieira, José PedroLopes, Fátima Daniela TeixeiraFernandes, Anabela SilvaSousa, Maria VâniaMoura, SofiaSousa, SusanaCosta, Bruno M.Barbosa, Mafalda Fernanda Cabral SantosYlstra, BaukeTemudo, TeresaLourenço, TeresaMaciel, P.2015-11-102015-11-10T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/51352engVieira, J. P., Lopes, F., Silva-Fernandes, A., Sousa, M. V., Moura, S., Sousa, S., ... & Lourenco, T. (2015). Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene. International Journal of Developmental Neuroscience, 46, 82-870736-574810.1016/j.ijdevneu.2015.07.01026287660https://www.sciencedirect.com/science/article/pii/S0736574815300277info: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:RCAAP2023-07-21T12:25:23Zoai:repositorium.sdum.uminho.pt:1822/51352Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:19:36.571649Repositório 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 |
Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene |
title |
Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene |
spellingShingle |
Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene Vieira, José Pedro Epigenetics Epilepsy Intellectual disability Neurodevelopment Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene |
title_full |
Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene |
title_fullStr |
Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene |
title_full_unstemmed |
Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene |
title_sort |
Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene |
author |
Vieira, José Pedro |
author_facet |
Vieira, José Pedro Lopes, Fátima Daniela Teixeira Fernandes, Anabela Silva Sousa, Maria Vânia Moura, Sofia Sousa, Susana Costa, Bruno M. Barbosa, Mafalda Fernanda Cabral Santos Ylstra, Bauke Temudo, Teresa Lourenço, Teresa Maciel, P. |
author_role |
author |
author2 |
Lopes, Fátima Daniela Teixeira Fernandes, Anabela Silva Sousa, Maria Vânia Moura, Sofia Sousa, Susana Costa, Bruno M. Barbosa, Mafalda Fernanda Cabral Santos Ylstra, Bauke Temudo, Teresa Lourenço, Teresa Maciel, P. |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Vieira, José Pedro Lopes, Fátima Daniela Teixeira Fernandes, Anabela Silva Sousa, Maria Vânia Moura, Sofia Sousa, Susana Costa, Bruno M. Barbosa, Mafalda Fernanda Cabral Santos Ylstra, Bauke Temudo, Teresa Lourenço, Teresa Maciel, P. |
dc.subject.por.fl_str_mv |
Epigenetics Epilepsy Intellectual disability Neurodevelopment Ciências Médicas::Medicina Básica Science & Technology |
topic |
Epigenetics Epilepsy Intellectual disability Neurodevelopment Ciências Médicas::Medicina Básica Science & Technology |
description |
Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome -46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated by the inversion. However, and in spite of a balanced pattern of X inactivation, this patient displayed hypomethylation and an overexpression of the MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55 +/- 038) in comparison to a group of control individuals; the expression of the CDKL5 gene was similar to that of controls (mean fold change: 0.98 +/- 0.10). No gains or losses were detected in the breakpoint regions encompassing known or suspected transcription regulatory elements. We propose that the de-regulation of MECP2 expression in this patient may be due to alterations in long-range genomic interactions caused by the inversion and hypothesize that this type of epigenetic de-regulation of the MECP2 may be present in other RTT-like patients. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-11-10 2015-11-10T00:00:00Z |
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/1822/51352 |
url |
http://hdl.handle.net/1822/51352 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Vieira, J. P., Lopes, F., Silva-Fernandes, A., Sousa, M. V., Moura, S., Sousa, S., ... & Lourenco, T. (2015). Variant Rett syndrome in a girl with a pericentric X-chromosome inversion leading to epigenetic changes and overexpression of the MECP2 gene. International Journal of Developmental Neuroscience, 46, 82-87 0736-5748 10.1016/j.ijdevneu.2015.07.010 26287660 https://www.sciencedirect.com/science/article/pii/S0736574815300277 |
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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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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1799132656043032576 |