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Molecular Medicine

, Volume 17, Issue 9–10, pp 875–882 | Cite as

Translational Research and Therapeutic Perspectives in Dysferlinopathies

  • Florian Barthélémy
  • Nicolas Wein
  • Martin Krahn
  • Nicolas Lévy
  • Marc Bartoli
Review Article

Abstract

Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene, encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B) and the second most common being LGMD. Symptoms generally appear at the end of childhood and, although disease progression is typically slow, walking impairments eventually result. Dysferlin is a modular type II transmembrane protein for which numerous binding partners have been identified. Although dysferlin function is only partially elucidated, this large protein contains seven calcium sensor C2 domains, shown to play a key role in muscle membrane repair. On the basis of this major function, along with detailed clinical observations, it has been possible to design various therapeutic approaches for dysferlin-deficient patients. Among them, exon-skipping and minigene transfer strategies have been evaluated at the preclinical level and, to date, represent promising approaches for clinical trials. This review aims to summarize the pathophysiology of dysferlinopathies and to evaluate the therapeutic potential for treatments currently under development.

Notes

Acknowledgments

We warmly acknowledge the constant support of the Association Française contre les Myopathies (AFM) and the Jain Foundation. F Barthélémy and N Wein received PhD fellowship grants from AFM and the Fondation pour la Recherche Médicale (FRM), respectively.

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Copyright information

© The Feinstein Institute for Medical Research 2011
www.feinsteininstitute.org

Authors and Affiliations

  • Florian Barthélémy
    • 1
    • 2
  • Nicolas Wein
    • 1
    • 2
  • Martin Krahn
    • 1
    • 2
    • 3
  • Nicolas Lévy
    • 1
    • 2
    • 3
  • Marc Bartoli
    • 1
    • 2
  1. 1.Marseille Medical SchoolUniversity of the MediterraneanMarseilleFrance
  2. 2.Faculté de Médecine de MarseilleUniversité de la Méditerranée, Inserm UMR_S 910 “Génétique Médicale et Génomique Fonctionnelle”MarseilleFrance
  3. 3.Department of Medical GeneticsMarseille Children’s HospitalMarseilleFrance

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