Ultrastructural changes in dysferlinopathy support defective membrane repair mechanism

• Published in: Journal of clinical pathology Vol. 58; no. 2; pp. 190 - 195
• Main Authors: Cenacchi, G, Fanin, M, De Giorgi, L B, Angelini, C
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.02.2005; BMJ; BMJ Publishing Group LTD; Copyright 2005 Journal of Clinical Pathology
• Subjects: Adolescent; Adult; Basement Membrane - pathology; Biological and medical sciences; Biopsy; Cloning; Dysferlin; Female; Gangrene; Gene expression; Humans; Immunoglobulins; Immunohistochemistry - methods; Inflammation; Investigative techniques, diagnostic techniques (general aspects); Labeling; LGMD; limb girdle muscular dystrophy; Lymphocytes; major histocompatibility class; Male; Medical sciences; Membrane Proteins - deficiency; Membrane Proteins - genetics; MHC; Microscopy; Microscopy, Electron - methods; Miyoshi myopathy; Morphology; Muscle Fibers, Skeletal - pathology; Muscle Fibers, Skeletal - physiology; Muscle Proteins - deficiency; Muscle Proteins - genetics; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscular Dystrophies - genetics; Muscular Dystrophies - pathology; Muscular Dystrophies - physiopathology; Musculoskeletal system; Mutation; Myositis - genetics; Myositis - pathology; Myositis - physiopathology; Original; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Patients; Sarcolemma - pathology; Sarcoplasmic Reticulum - pathology; California; Membrane; Anatomic pathology; Support; Repair; Ultrastructure; Mechanism
• ISSN: 0021-9746; 1472-4146
• DOI: 10.1136/jcp.2004.018978

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. Aims: 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.