A third of LGMD2A biopsies have normal calpain 3 proteolytic activity as determined by an in vitro assay

Astrid Milic, Nathalie Daniele, Hanns Lochmüller, Marina Mora, Giacomo P. Comi, Maurizio Moggio, Fanny Noulet, Maggie C. Walter, Lucia Morandi, Jérôme Poupiot, Carinne Roudaut, Reginald E. Bittner, Marc Bartoli, Isabelle Richard

Research output: Contribution to journalArticle

Abstract

Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive muscular disorder caused by mutations in the gene coding for calpain 3, a calcium-dependent protease. We developed an in vitro assay that can detect the proteolytic activity of calpain 3 in a muscle sample. This assay is based on the use of an inactive calpain 3 as a substrate for active calpain 3 molecules. A total of 79 human biopsies have been analysed using an unbiased single blind method. Results were confronted with the molecular diagnosis for confirmation. Proteolytic activity was either reduced or absent in 68% of LGMD2A biopsies. In the remaining 32%, normal proteolytic activity was found despite the presence of calpain 3 mutation(s), suggesting that other calpain 3 properties might be impaired to give rise to the LGMD2A phenotype. Our assay is easily adaptable to routine and appears to be more sensitive than common analysis by immunodetection.

Original languageEnglish
Pages (from-to)148-156
Number of pages9
JournalNeuromuscular Disorders
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 2007

Keywords

  • Calpain 3 proteolytic activity
  • Diagnosis
  • Dysferlin
  • LGMD2A

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

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  • Cite this

    Milic, A., Daniele, N., Lochmüller, H., Mora, M., Comi, G. P., Moggio, M., Noulet, F., Walter, M. C., Morandi, L., Poupiot, J., Roudaut, C., Bittner, R. E., Bartoli, M., & Richard, I. (2007). A third of LGMD2A biopsies have normal calpain 3 proteolytic activity as determined by an in vitro assay. Neuromuscular Disorders, 17(2), 148-156. https://doi.org/10.1016/j.nmd.2006.11.001