Journal Article

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

Caparros-Martin, José A., Lapunzina, Pablo, Bönnemann, Carsten G., Chao, Katherine Ru-Yui, Hu, Ying, Aglan, Mona, Nevado, Julián, Largo, Raquel, Martinez-Glez, Victor, Issa, Mahmoud, Carvajal, Jaime J., Esteban, María Isabel, Herrero-Beaumont, Gabriel, Nelson, David L., Fernández-Núñez, Elisa, Temtamy, Samia, Hawkins, Cynthia, Bolduc, Véronique, Hernandez-Chico, Concepción, Saade, Dimah, Zong, Ruiting, Estañ, María Cristina, Donkervoort, Sandra, Tizzano, Eduardo F., Ruiz-Perez, Victor L., Regadera, Javier, Lamuedra, Ana, Otaify, Ghada A., Yoon, Grace, Zaki, Maha S.

2019

Overview

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. FXR1P is a RNA binding protein involved in muscle development. Here, the authors show that mutations in FXR1 exon 15, which is alternatively spliced in muscle, cause multi-minicore myopathy in humans and in mouse models.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 14 / 14/19 / 14/28 / 14/32 / 14/63 / 38/70 / 38/91 / 59 / 59/57 / 631/208/2489 / 64 / 64/60 / 692/308/1426 / 692/699/375/374 / 82/1 / Alternative splicing / Animals / Cells, Cultured / Depletion / Exons - genetics / Gene Expression / Genes, Recessive / Genetic Predisposition to Disease - genetics / HEK293 Cells / HeLa Cells / Humanities and Social Sciences / Humans / Isoforms / Mice / Mice, Transgenic / multidisciplinary / Muscle, Skeletal - metabolism / Muscles / Mutation / Myopathies, Structural, Congenital - congenital / Myopathies, Structural, Congenital - genetics / Myopathies, Structural, Congenital - metabolism / Myopathy / Neonates / Ophthalmoplegia - congenital / Ophthalmoplegia - genetics / Ophthalmoplegia - metabolism / Proteins / Ribonucleic acid / RNA / RNA-binding protein / 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 / Science / Science (multidisciplinary) / Skeletal muscle