Mutations in JMJD1C are involved in Rett syndrome and intellectual disability
Purpose: autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/113221 |
| Acceso en línea: | https://hdl.handle.net/2445/113221 |
| Access Level: | acceso abierto |
| Palabra clave: | Síndrome de Rett Discapacitats mentals Autisme Trastorns de l'espectre autista Mutació (Biologia) Rett syndrome People with mental disabilities Autism Autism spectrum disorders Mutation (Biology) |
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Mutations in JMJD1C are involved in Rett syndrome and intellectual disabilitySáez, Mauricio A.Fernández Rodríguez, JuanaMoutinho, CátiaSanchez-Mut, Jose VicenteGómez, AntonioVidal, EnriquePetazzi, PaoloSzczesna, KarolinaLópez Serra, PaulaLucariello, MarioLorden, PatriciaDelgado-Morales, RaulCaridad, Olga J. de laHuertas, DoriGelpí Buchaca, Josep LluísOrozco López, ModestoLópez Dóriga Guerra, AdrianaMilà i Recasens, MontserratPérez Jurado, Luis A.Pineda, MercedesArmstrong i Morón, JudithLázaro García, ConxiEsteller, ManelSíndrome de RettDiscapacitats mentalsAutismeTrastorns de l'espectre autistaMutació (Biologia)Rett syndromePeople with mental disabilitiesAutismAutism spectrum disordersMutation (Biology)Purpose: autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders. Methods: we performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect. Results: we found seven JMJD1C variants that were not present in any control sample (~ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity. Conclusions: our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability.American College of Medical Genetics and Genomics2017201720162017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion8 p.application/pdfhttps://hdl.handle.net/2445/113221Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/gim.2015.100Genetics in Medicine, 2016, vol. 18, num. 4, p. 378-385https://doi.org/10.1038/gim.2015.100info:eu-repo/grantAgreement/EC/FP7/268626info:eu-repo/grantAgreement/EC/FP7/316758info:eu-repo/grantAgreement/EC/FP7/238242cc-by-nc-nd (c) Sáez, Mauricio A. et al., 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1132212026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Mutations in JMJD1C are involved in Rett syndrome and intellectual disability |
| title |
Mutations in JMJD1C are involved in Rett syndrome and intellectual disability |
| spellingShingle |
Mutations in JMJD1C are involved in Rett syndrome and intellectual disability Sáez, Mauricio A. Síndrome de Rett Discapacitats mentals Autisme Trastorns de l'espectre autista Mutació (Biologia) Rett syndrome People with mental disabilities Autism Autism spectrum disorders Mutation (Biology) |
| title_short |
Mutations in JMJD1C are involved in Rett syndrome and intellectual disability |
| title_full |
Mutations in JMJD1C are involved in Rett syndrome and intellectual disability |
| title_fullStr |
Mutations in JMJD1C are involved in Rett syndrome and intellectual disability |
| title_full_unstemmed |
Mutations in JMJD1C are involved in Rett syndrome and intellectual disability |
| title_sort |
Mutations in JMJD1C are involved in Rett syndrome and intellectual disability |
| dc.creator.none.fl_str_mv |
Sáez, Mauricio A. Fernández Rodríguez, Juana Moutinho, Cátia Sanchez-Mut, Jose Vicente Gómez, Antonio Vidal, Enrique Petazzi, Paolo Szczesna, Karolina López Serra, Paula Lucariello, Mario Lorden, Patricia Delgado-Morales, Raul Caridad, Olga J. de la Huertas, Dori Gelpí Buchaca, Josep Lluís Orozco López, Modesto López Dóriga Guerra, Adriana Milà i Recasens, Montserrat Pérez Jurado, Luis A. Pineda, Mercedes Armstrong i Morón, Judith Lázaro García, Conxi Esteller, Manel |
| author |
Sáez, Mauricio A. |
| author_facet |
Sáez, Mauricio A. Fernández Rodríguez, Juana Moutinho, Cátia Sanchez-Mut, Jose Vicente Gómez, Antonio Vidal, Enrique Petazzi, Paolo Szczesna, Karolina López Serra, Paula Lucariello, Mario Lorden, Patricia Delgado-Morales, Raul Caridad, Olga J. de la Huertas, Dori Gelpí Buchaca, Josep Lluís Orozco López, Modesto López Dóriga Guerra, Adriana Milà i Recasens, Montserrat Pérez Jurado, Luis A. Pineda, Mercedes Armstrong i Morón, Judith Lázaro García, Conxi Esteller, Manel |
| author_role |
author |
| author2 |
Fernández Rodríguez, Juana Moutinho, Cátia Sanchez-Mut, Jose Vicente Gómez, Antonio Vidal, Enrique Petazzi, Paolo Szczesna, Karolina López Serra, Paula Lucariello, Mario Lorden, Patricia Delgado-Morales, Raul Caridad, Olga J. de la Huertas, Dori Gelpí Buchaca, Josep Lluís Orozco López, Modesto López Dóriga Guerra, Adriana Milà i Recasens, Montserrat Pérez Jurado, Luis A. Pineda, Mercedes Armstrong i Morón, Judith Lázaro García, Conxi Esteller, Manel |
| 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.subject.none.fl_str_mv |
Síndrome de Rett Discapacitats mentals Autisme Trastorns de l'espectre autista Mutació (Biologia) Rett syndrome People with mental disabilities Autism Autism spectrum disorders Mutation (Biology) |
| topic |
Síndrome de Rett Discapacitats mentals Autisme Trastorns de l'espectre autista Mutació (Biologia) Rett syndrome People with mental disabilities Autism Autism spectrum disorders Mutation (Biology) |
| description |
Purpose: autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders. Methods: we performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect. Results: we found seven JMJD1C variants that were not present in any control sample (~ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity. Conclusions: our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability. |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016 2017 2017 2017 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/113221 |
| url |
https://hdl.handle.net/2445/113221 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1038/gim.2015.100 Genetics in Medicine, 2016, vol. 18, num. 4, p. 378-385 https://doi.org/10.1038/gim.2015.100 info:eu-repo/grantAgreement/EC/FP7/268626 info:eu-repo/grantAgreement/EC/FP7/316758 info:eu-repo/grantAgreement/EC/FP7/238242 |
| dc.rights.none.fl_str_mv |
cc-by-nc-nd (c) Sáez, Mauricio A. et al., 2016 http://creativecommons.org/licenses/by-nc-nd/3.0/es info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc-nd (c) Sáez, Mauricio A. et al., 2016 http://creativecommons.org/licenses/by-nc-nd/3.0/es |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
8 p. application/pdf |
| dc.publisher.none.fl_str_mv |
American College of Medical Genetics and Genomics |
| publisher.none.fl_str_mv |
American College of Medical Genetics and Genomics |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Ciències Fisiològiques) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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