Sarcolemmal reorganization in facioscapulohumeral muscular dystrophy

• Published in: Annals of neurology Vol. 59; no. 2; pp. 289 - 297
• Main Authors: Reed, Patrick, Porter, Neil C., Strong, John, Pumplin, David W., Corse, Andrea M., Luther, Paul W., Flanigan, Kevin M., Bloch, Robert J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2006
• Subjects: Cytoskeleton - physiology; Fluorescent Antibody Technique - methods; Humans; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal - ultrastructure; Muscular Dystrophy, Facioscapulohumeral - pathology; Muscular Dystrophy, Facioscapulohumeral - physiopathology; Sarcolemma - metabolism; Sarcolemma - physiology; Sarcolemma - ultrastructure; Spectrin - metabolism
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.20750

Objective We examined the sarcolemma of skeletal muscle from patients with facioscapulohumeral muscular dystrophy (FSHD1A) to learn if, as in other murine and human muscular dystrophies, its organization and relationship to nearby contractile structures are altered. Methods Unfixed biopsies of control and FSHD deltoid and biceps muscles, snap‐frozen at resting length, were cryosectioned, indirectly immunolabeled with fluorescent antibodies to sarcolemmal and myofibrillar markers, and examined with confocal microscopy to localize the immunolabeled proteins. Glutaraldehyde‐fixed samples were stained with heavy metals, embedded, thin‐sectioned, and examined with electron microscopy to determine the relationship between the sarcolemma and the underlying myofibrils. Results Confocal microscopy showed that some of the structures at the sarcolemma in FSHD samples were misaligned with respect to the underlying contractile apparatus. Electron microscopy showed a significant increase in the distance between the sarcolemma and the nearest myofibrils, from less than 100nm in controls to values as high as 550nm in FSHD. Interpretation Our results show that the pathophysiology of FSHD includes novel changes in the organization of the sarcolemma and its association with nearby contractile structures and suggest that, as in other muscular dystrophies, the integrity of the sarcolemma may be compromised in FSHD. Ann Neurol 2006;59:289–297