Research ArticleMuscular Dystrophy

A Naturally Occurring Human Minidysferlin Protein Repairs Sarcolemmal Lesions in a Mouse Model of Dysferlinopathy

See allHide authors and affiliations

Science Translational Medicine  22 Sep 2010:
Vol. 2, Issue 50, pp. 50ra69
DOI: 10.1126/scitranslmed.3000951

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution


Dysferlinopathies are autosomal recessive, progressive muscle dystrophies caused by mutations in DYSF, leading to a loss or a severe reduction of dysferlin, a key protein in sarcolemmal repair. Currently, no etiological treatment is available for patients affected with dysferlinopathy. As for other muscular dystrophies, gene therapy approaches based on recombinant adeno-associated virus (rAAV) vectors are promising options. However, because dysferlin messenger RNA is far above the natural packaging size of rAAV, full-length dysferlin gene transfer would be problematic. In a patient presenting with a late-onset moderate dysferlinopathy, we identified a large homozygous deletion, leading to the production of a natural “minidysferlin” protein. Using rAAV-mediated gene transfer into muscle, we demonstrated targeting of the minidysferlin to the muscle membrane and efficient repair of sarcolemmal lesions in a mouse model of dysferlinopathy. Thus, as previously demonstrated in the case of dystrophin, a deletion mutant of the dysferlin gene is also functional, suggesting that dysferlin’s structure is modular. This minidysferlin protein could be used as part of a therapeutic strategy for patients affected with dysferlinopathies.


  • * These authors contributed equally to this work.

  • Citation: M. Krahn, N. Wein, M. Bartoli, W. Lostal, S. Courrier, N. Bourg-Alibert, K. Nguyen, C. Vial, N. Streichenberger, V. Labelle, D. DePetris, C. Pécheux, F. Leturcq, P. Cau, I. Richard, N. Lévy, A Naturally Occurring Human Minidysferlin Protein Repairs Sarcolemmal Lesions in a Mouse Model of Dysferlinopathy. Sci. Transl. Med. 2, 50ra69 (2010).

View Full Text

Stay Connected to Science Translational Medicine