| Title: |
Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy |
| Authors: |
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. |
| Contributors: |
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) |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2019 |
| Collection: |
Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
| Subject Terms: |
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. ; 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Nature Communications; https://doi.org/10.1038/s41467-019-08548-9; Gobierno de España. SAF2013-43365- R; Gobierno de España. SAF2016-75434-R; Nature Communications 10.1 (2019): 797; https://hdl.handle.net/10486/688388; 10 |
| DOI: |
10.1038/s41467-019-08548-9 |
| Availability: |
https://hdl.handle.net/10486/688388; https://doi.org/10.1038/s41467-019-08548-9 |
| Rights: |
© 2019, The Author(s) ; Reconocimiento ; open access |
| Accession Number: |
edsbas.E6A0E3A1 |
| Database: |
BASE |