Article Text

Download PDFPDF
Alteration of expression of muscle specific isoforms of the fragile X related protein 1 (FXR1P) in facioscapulohumeral muscular dystrophy patients
  1. L Davidovic1,
  2. S Sacconi2,
  3. E G Bechara1,
  4. S Delplace2,
  5. M Allegra2,
  6. C Desnuelle2,
  7. B Bardoni1
  1. 1
    Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR6097, Université de Nice Sophia-Antipolis, Valbonne, France
  2. 2
    INSERM U638 Faculté de Médecine, Université de Nice Sophia-Antipolis, Centre de Référence pour les Maladies Neuromusculaires, CHU de Nice, Nice, France
  1. Dr B Bardoni, Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR6097, Université de Nice Sophia-Antipolis - 660, Route des Lucioles, 06160 Valbonne, France; bardoni{at}


Background: The Fragile X Mental retardation-Related 1 (FXR1) gene belongs to the fragile X related family, that also includes the Fragile X Mental Retardation (FMR1) gene involved in fragile X syndrome, the most common form of inherited mental retardation. While the absence of FMRP impairs cognitive functions, inactivation of FXR1 has been reported to have drastic effects in mouse and xenopus myogenesis. Seven alternatively spliced FXR1 mRNA variants have been identified, three of them being muscle specific. Interestingly, they encode FXR1P isoforms displaying selective RNA binding properties.

Methods and results: Since facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy characterised by altered splicing of mRNAs encoding muscle specific proteins, we have studied the splicing pattern of FXR1 mRNA in myoblasts and myotubes of FSHD patients. We show here that FSHD myoblasts display an abnormal pattern of expression of FXR1P isoforms. Moreover, we provide evidence that this altered pattern of expression is due to a specific reduced stability of muscle specific FXR1 mRNA variants, leading to a reduced expression of FXR1P muscle specific isoforms.

Conclusion: Our data suggest that the molecular basis of FSHD not only involves splicing alterations, as previously proposed, but may also involve a deregulation of mRNA stability. In addition, since FXR1P is an RNA binding protein likely to regulate the metabolism of muscle specific mRNAs during myogenesis, its altered expression in FSHD myoblasts may contribute to the physiopathology of this disease.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding:This study was supported by INSERM, CNRS, CHU de Nice, Agence Nationale de la Recherche, GIS-Maladies Rares. FSHD group is financed by Association Française Contre les Myopathies (CD and SS). LD is a recipient of a fellowship from “Marie Curie Mobility Program”. EGB is supported by Fondation pour la Recherche Médicale.

  • Competing interests: None declared.

  • Patient consent: Obtained.