title: Ultrastructural changes in dysferlinopathy support defective membrane repair mechanism.
abstract: BACKGROUND
  The dysferlin gene has recently been shown to be involved in limb girdle muscular dystrophy type 2B and its allelic disease, Miyoshi myopathy, both of which are characterised by an active muscle degeneration and regeneration process. Dysferlin is known to play an essential role in skeletal muscle fibre repair, but the process underlying the pathogenetic mechanism of dysferlinopathy is not completely understood.
  
  
  OBJECTIVE
  To define both specific alterations of muscle fibres and a possible sequential mechanism of myopathy development.
  
  
  METHODS
  A histological, immunohistochemical, and ultrastructural analysis of 10 muscle biopsies from patients with molecularly diagnosed dysferlinopathy.
  
  
  RESULTS
  An inflammatory response was seen in most of the muscle biopsies. The immunohistochemical pattern demonstrated active regeneration and inflammation. Non-necrotic fibres showed alterations at different submicroscopic levels, namely: the sarcolemma and basal lamina, subsarcolemmal region, and sarcoplasmic compartment. In the subsarcolemmal region there were prominent aggregations of small vesicles, probably derived from the Golgi apparatus, which consisted of empty, swollen cisternae. In the sarcolemma there were many gaps and microvilli-like projections, whereas the basal lamina was multilayered.
  
  
  CONCLUSIONS
  The histopathological, immunohistochemical, and ultrastructural data show that dysferlinopathy is characterised by a very active inflammatory/degenerative process, possibly associated with an inefficient repair and regenerative system. The presence of many crowded vesicles just beneath the sarcolemma provides submicroscopical proof of a defective resealing mechanism, which fails to repair the sarcolemma.
authors.affiliation: Clinical Department of Radiological and Histocytopathological Sciences, University of Bologna, 40138 Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cenacchi
authors.forename: M
authors.initials: M
authors.lastname: Fanin
authors.forename: L B
authors.initials: LB
authors.lastname: De Giorgi
authors.forename: C
authors.initials: C
authors.lastname: Angelini
mesh_terms: D000293:Adolescent; D000328:Adult; D001485:Basement Membrane / Q000473:pathology; D000073939:Dysferlin; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D008854:Microscopy, Electron / Q000379:methods; D018485:Muscle Fibers, Skeletal / Q000473:pathology* / Q000502:physiology; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009220:Myositis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012508:Sarcolemma / Q000473:pathology; D012519:Sarcoplasmic Reticulum / Q000473:pathology
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins