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Recessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy
Journal article   Open access   Peer reviewed

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

María Cristina Estañ, Elisa Fernández-Núñez, Maha S Zaki, María Isabel Esteban, Sandra Donkervoort, Cynthia Hawkins, José A Caparros-Martin, Dimah Saade, Ying Hu, Véronique Bolduc, …
Nature communications, Vol.10(1), pp.797-797
02/15/2019
DOI: 10.1038/s41467-019-08548-9
PMCID: PMC6377633
PMID: 30770808
url
https://doi.org/10.1038/s41467-019-08548-9View
Published (Version of record) Open Access

Abstract

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.
Gene Expression Mutation Animals Cells, Cultured Exons - genetics Genes, Recessive Genetic Predisposition to Disease - genetics HEK293 Cells HeLa Cells Humans Mice, Transgenic Muscle, Skeletal - metabolism Myopathies, Structural, Congenital - congenital Myopathies, Structural, Congenital - genetics Myopathies, Structural, Congenital - metabolism Ophthalmoplegia - congenital Ophthalmoplegia - genetics Ophthalmoplegia - metabolism RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Ryanodine Receptor Calcium Release Channel - deficiency Ryanodine Receptor Calcium Release Channel - genetics Ryanodine Receptor Calcium Release Channel - metabolism

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