Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy

FXR1 is an alternatively spliced gene that encodes RNA binding proteins (FXR1P) involved in muscle development. In contrast to other tissues, cardiac and skeletal muscle express two FXR1P isoforms that incorporate an additional exon-15. We report that recessive mutations in this particular exon of F...

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Autores: Estañ, María Cristina, Fernández-Núñez, Elisa, Zaki, Maha S., Esteban, María Isabel, Donkervoort, Sandra, Hawkins, Cynthia, Caparros-Martin, José A., Saade, Dimah, Hu, Ying, Bolduc, Véronique, Chao, Katherine Ru Yui, Nevado, Julián, Lamuedra, Ana, Largo, Raquel, Herrero-Beaumont Cuenca, Gabriel, Regadera, Javier, Hernandez-Chico, Concepción, Tizzano, Eduardo F., Martinez-Glez, Victor, Carvajal, Jaime J., Zong, Ruiting, Nelson, David L., Otaify, Ghada A., Temtamy, Samia, Aglan, Mona, Issa, Mahmoud, Bönnemann, Carsten G., Lapunzina, Pablo, Yoon, Grace, Ruiz-Perez, Victor L.
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/688388
Acceso en línea:http://hdl.handle.net/10486/688388
https://dx.doi.org/10.1038/s41467-019-08548-9
Access Level:acceso abierto
Palabra clave:FXR1
FXR1P
Recessive mutations
Myopath
Protein
Medicina
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network_name_str España
repository_id_str
spelling Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathyEstañ, María CristinaFernández-Núñez, ElisaZaki, Maha S.Esteban, María IsabelDonkervoort, SandraHawkins, CynthiaCaparros-Martin, José A.Saade, DimahHu, YingBolduc, VéroniqueChao, Katherine Ru YuiNevado, JuliánLamuedra, AnaLargo, RaquelHerrero-Beaumont Cuenca, GabrielRegadera, JavierHernandez-Chico, ConcepciónTizzano, Eduardo F.Martinez-Glez, VictorCarvajal, Jaime J.Zong, RuitingNelson, David L.Otaify, Ghada A.Temtamy, SamiaAglan, MonaIssa, MahmoudBönnemann, Carsten G.Lapunzina, PabloYoon, GraceRuiz-Perez, Victor L.FXR1FXR1PRecessive mutationsMyopathProteinMedicinaFXR1 is an alternatively spliced gene that encodes RNA binding proteins (FXR1P) involved in muscle development. In contrast to other tissues, cardiac and skeletal muscle express two FXR1P isoforms that incorporate an additional exon-15. We report that recessive mutations in this particular exon of FXR1 cause congenital multi-minicore myopathy in humans and mice. Additionally, we show that while Myf5-dependent depletion of all FXR1P isoforms is neonatal lethal, mice carrying mutations in exon-15 display non-lethal myopathies which vary in severity depending on the specific effect of each mutation on the protein.This work was financially supported by the Spanish Ministry of Economy and Competitiveness (SAF2013-43365- R/SAF2016-75434-R) and CIBERER (ACCI 2017). The work performed at the NIH was supported by intramural funds from the NIH National Institute of Neurological Disorders and Stroke. Sequencing analysis was provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics and was funded by the National Human Genome Research Institute, the National Eye Institute and the National Heart, Lung and Blood Institute grant UM1 HG008900 to Daniel MacArthur and Heidi Rehm. The Broad Center for Mendelian Genomics (UM1 HG008900) is funded by the National Human Genome Research Institute with supplemental funding provided by the National Heart, Lung, and Blood Institute under the Trans-Omics for Precision Medicine (TOPMed) program and the National Eye Institute.Springer NatureDepartamento de Anatomía, Histología y NeurocienciaDepartamento de MedicinaFacultad de MedicinaInstituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)20192019-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/688388https://dx.doi.org/10.1038/s41467-019-08548-9reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6883882026-06-23T12:46:27Z
dc.title.none.fl_str_mv Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
title Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
spellingShingle Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
Estañ, María Cristina
FXR1
FXR1P
Recessive mutations
Myopath
Protein
Medicina
title_short Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
title_full Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
title_fullStr Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
title_full_unstemmed Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
title_sort Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
dc.creator.none.fl_str_mv Estañ, María Cristina
Fernández-Núñez, Elisa
Zaki, Maha S.
Esteban, María Isabel
Donkervoort, Sandra
Hawkins, Cynthia
Caparros-Martin, José A.
Saade, Dimah
Hu, Ying
Bolduc, Véronique
Chao, Katherine Ru Yui
Nevado, Julián
Lamuedra, Ana
Largo, Raquel
Herrero-Beaumont Cuenca, Gabriel
Regadera, Javier
Hernandez-Chico, Concepción
Tizzano, Eduardo F.
Martinez-Glez, Victor
Carvajal, Jaime J.
Zong, Ruiting
Nelson, David L.
Otaify, Ghada A.
Temtamy, Samia
Aglan, Mona
Issa, Mahmoud
Bönnemann, Carsten G.
Lapunzina, Pablo
Yoon, Grace
Ruiz-Perez, Victor L.
author Estañ, María Cristina
author_facet Estañ, María Cristina
Fernández-Núñez, Elisa
Zaki, Maha S.
Esteban, María Isabel
Donkervoort, Sandra
Hawkins, Cynthia
Caparros-Martin, José A.
Saade, Dimah
Hu, Ying
Bolduc, Véronique
Chao, Katherine Ru Yui
Nevado, Julián
Lamuedra, Ana
Largo, Raquel
Herrero-Beaumont Cuenca, Gabriel
Regadera, Javier
Hernandez-Chico, Concepción
Tizzano, Eduardo F.
Martinez-Glez, Victor
Carvajal, Jaime J.
Zong, Ruiting
Nelson, David L.
Otaify, Ghada A.
Temtamy, Samia
Aglan, Mona
Issa, Mahmoud
Bönnemann, Carsten G.
Lapunzina, Pablo
Yoon, Grace
Ruiz-Perez, Victor L.
author_role author
author2 Fernández-Núñez, Elisa
Zaki, Maha S.
Esteban, María Isabel
Donkervoort, Sandra
Hawkins, Cynthia
Caparros-Martin, José A.
Saade, Dimah
Hu, Ying
Bolduc, Véronique
Chao, Katherine Ru Yui
Nevado, Julián
Lamuedra, Ana
Largo, Raquel
Herrero-Beaumont Cuenca, Gabriel
Regadera, Javier
Hernandez-Chico, Concepción
Tizzano, Eduardo F.
Martinez-Glez, Victor
Carvajal, Jaime J.
Zong, Ruiting
Nelson, David L.
Otaify, Ghada A.
Temtamy, Samia
Aglan, Mona
Issa, Mahmoud
Bönnemann, Carsten G.
Lapunzina, Pablo
Yoon, Grace
Ruiz-Perez, Victor L.
author2_role author
author
author
author
author
author
author
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 Departamento de Anatomía, Histología y Neurociencia
Departamento de Medicina
Facultad de Medicina
Instituto de Investigaciones Biomédicas "Alberto Sols" (IIBM)
Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)
Instituto de Investigación Sanitaria del Hospital Universitario de La Paz (IdiPAZ)
dc.subject.none.fl_str_mv FXR1
FXR1P
Recessive mutations
Myopath
Protein
Medicina
topic FXR1
FXR1P
Recessive mutations
Myopath
Protein
Medicina
description FXR1 is an alternatively spliced gene that encodes RNA binding proteins (FXR1P) involved in muscle development. In contrast to other tissues, cardiac and skeletal muscle express two FXR1P isoforms that incorporate an additional exon-15. We report that recessive mutations in this particular exon of FXR1 cause congenital multi-minicore myopathy in humans and mice. Additionally, we show that while Myf5-dependent depletion of all FXR1P isoforms is neonatal lethal, mice carrying mutations in exon-15 display non-lethal myopathies which vary in severity depending on the specific effect of each mutation on the protein.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/688388
https://dx.doi.org/10.1038/s41467-019-08548-9
url http://hdl.handle.net/10486/688388
https://dx.doi.org/10.1038/s41467-019-08548-9
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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