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

TitleRecessive mutations in muscle-specific isoforms of FXR1 cause congenital multi-minicore myopathy.
Publication TypeJournal Article
Year of Publication2019
AuthorsEstañ, MCristina, Fernández-Núñez, E, Zaki, MS, Esteban, MIsabel, Donkervoort, S, Hawkins, C, Caparros-Martin, JA, Saade, D, Hu, Y, Bolduc, V, Chao, KRu-Yui, Nevado, J, Lamuedra, A, Largo, R, Herrero-Beaumont, G, Regadera, J, Hernandez-Chico, C, Tizzano, EF, Martinez-Glez, V, Carvajal, JJ, Zong, R, Nelson, DL, Otaify, GA, Temtamy, S, Aglan, M, Issa, M, Bönnemann, CG, Lapunzina, P, Yoon, G, Ruiz-Perez, VL
JournalNat Commun
Date Published2019 02 15
KeywordsAnimals, Cells, Cultured, Exons, Gene Expression, Genes, Recessive, Genetic Predisposition to Disease, HEK293 Cells, HeLa Cells, Humans, Mice, Transgenic, Muscle, Skeletal, Mutation, Myopathies, Structural, Congenital, Ophthalmoplegia, RNA-Binding Proteins, Ryanodine Receptor Calcium Release Channel

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.

Alternate JournalNat Commun
PubMed ID30770808
PubMed Central IDPMC6377633
Grant ListUM1 HG008900 / HG / NHGRI NIH HHS / United States