Calpain-3 and dysferlin protein screening in patients with limb-girdle dystrophy and myopathy

M. Fanin, E. Pegoraro, C. Matsuda-Asada, R. H. Brown, C. Angelini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Mutations in the genes encoding for calpain-3 and dysferlin are responsible for limb girdle muscular dystrophy (LGMD) type 2A and 2B, the most common forms of autosomal recessive LGMD. Objective: To identify calpain-3 or dysferlin deficiency in a large cohort of patients with as yet unclassified LGMD and myopathy through candidate protein analysis. Methods: The authors' muscle biopsy database search identified 407 candidate muscle biopsies with normal dystrophin and sarcoglycan. Calpain-3 and dysferlin were studied by Western blotting and immunohistochemistry. Results: Combined calpain-3 and dysferlin Western blot analysis identified calpain-3 deficiency in 66 (16%) muscle biopsies. In 31 cases (47%), the protein was absent, and in 35 (53%), it was severely reduced in amount (3 to 50% of control). Dysferlin deficiency was found in 26 (6.5%) muscle biopsies. In 9, the protein was absent (35%), and in 17 (65%), it was severely reduced in amount (traces to 20% of control). Twenty-eight percent (53/191) of patients with LGMD phenotype had calpain-3 deficiency. Sixty percent (21/35) of patients with distal myopathy had dysferlin deficiency. Dysferlin immunohistochemistry showed, in the completely dysferlin-deficient patients, absent reaction at the sarcolemma but positive nuclear membrane labeling and, in the partially dysferlin-deficient patients, scattered granular positive cytoplasmic areas and diffuse reaction in regenerating fibers. Conclusion: About 25% of previously unclassified dystrophy/myopathy cases are due to calpain-3 or dysferlin protein deficiency. These results suggest that immunoblot analysis may be used to define patients for calpain-3 and dysferlin gene mutation studies.

Original languageEnglish
Pages (from-to)660-665
Number of pages6
JournalNeurology
Volume56
Issue number5
Publication statusPublished - Mar 13 2001

ASJC Scopus subject areas

  • Neuroscience(all)

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