Secondary reduction in calpain 3 expression in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies)

Dysferlin is the protein product of the gene ( DYSF) that is defective in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy. Calpain 3 is the muscle-specific member of the calcium activated neutral protease family and primary mutations in the CAPN3 gene cause limb girdle musc...

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Bibliographic Details
Published in:Neuromuscular disorders : NMD 2000-12, Vol.10 (8), p.553-559
Main Authors: Anderson, Louise V.B, Harrison, Ruth M, Pogue, Robert, Vafiadaki, Elizabeth, Pollitt, Christine, Davison, Keith, Moss, Jennifer A, Keers, Sharon, Pyle, Angela, Shaw, Pamela J, Mahjneh, Ibrahim, Argov, Zohar, Greenberg, Cheryl R, Wrogemann, Klaus, Bertorini, Tulio, Goebel, Hans H, Beckmann, Jacques S, Bashir, Rumaisa, Bushby, Kate M.D
Format: Article
Language:English
Subjects:
Calpain - deficiency
Calpain - genetics
Calpain 3
DNA Mutational Analysis
Dysferlin
Humans
Laminin
Membrane Proteins
Merosin
Muscle proteins
Muscle Proteins - deficiency
Muscle Proteins - genetics
Muscular Diseases - enzymology
Muscular Diseases - genetics
Muscular Dystrophies - enzymology
Muscular Dystrophies - genetics
Muscular dystrophy
Western blotting
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Summary:Dysferlin is the protein product of the gene ( DYSF) that is defective in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy. Calpain 3 is the muscle-specific member of the calcium activated neutral protease family and primary mutations in the CAPN3 gene cause limb girdle muscular dystrophy type 2A. The functions of both proteins remain speculative. Here we report a secondary reduction in calpain 3 expression in eight out of 16 patients with a primary dysferlinopathy and clinical features characteristic of limb girdle muscular dystrophy type 2B or Miyoshi myopathy. Previously CAPN3 analysis had been undertaken in three of these patients and two showed seemingly innocuous missense mutations, changing calpain 3 amino acids to those present in the sequences of calpains 1 and 2. These results suggest that there may be an association between dysferlin and calpain 3, and further analysis of both genes may elucidate a novel functional interaction. In addition, an association was found between prominent expression of smaller forms of the 80 kDa fragment of laminin α2 chain (merosin) and dysferlin-deficiency.
ISSN:0960-8966
1873-2364
DOI:10.1016/S0960-8966(00)00143-7