title: Secondary reduction in calpain 3 expression in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies).
abstract: 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 alpha 2 chain (merosin) and dysferlin-deficiency.
authors.affiliation: Neurobiology Department, University Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. l.v.b.anderson@ncl.ac.uk
authors.forename: L V
authors.initials: LV
authors.lastname: Anderson
authors.forename: R M
authors.initials: RM
authors.lastname: Harrison
authors.forename: R
authors.initials: R
authors.lastname: Pogue
authors.forename: E
authors.initials: E
authors.lastname: Vafiadaki
authors.forename: C
authors.initials: C
authors.lastname: Pollitt
authors.forename: K
authors.initials: K
authors.lastname: Davison
authors.forename: J A
authors.initials: JA
authors.lastname: Moss
authors.forename: S
authors.initials: S
authors.lastname: Keers
authors.forename: A
authors.initials: A
authors.lastname: Pyle
authors.forename: P J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: I
authors.initials: I
authors.lastname: Mahjneh
authors.forename: Z
authors.initials: Z
authors.lastname: Argov
authors.forename: C R
authors.initials: CR
authors.lastname: Greenberg
authors.forename: K
authors.initials: K
authors.lastname: Wrogemann
authors.forename: T
authors.initials: T
authors.lastname: Bertorini
authors.forename: H H
authors.initials: HH
authors.lastname: Goebel
authors.forename: J S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: R
authors.initials: R
authors.lastname: Bashir
authors.forename: K M
authors.initials: KM
authors.lastname: Bushby
mesh_terms: D002154:Calpain / Q000172:deficiency* / Q000235:genetics; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D006801:Humans; D008565:Membrane Proteins; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics; D009135:Muscular Diseases / Q000201:enzymology* / Q000235:genetics; D009136:Muscular Dystrophies / Q000201:enzymology* / Q000235:genetics
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D002154:Calpain