Publication year
2013Source
Neurology, 80, 8, (2013), pp. 733-7ISSN
Publication type
Article / Letter to editor
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Organization
Neurology
Human Genetics
Pulmonary Diseases
Journal title
Neurology
Volume
vol. 80
Issue
iss. 8
Page start
p. 733
Page end
p. 7
Subject
DCN MP - Plasticity and memory; DCN MP - Plasticity and memory NCEBP 10: Human Movement & FatigueAbstract
OBJECTIVE: To investigate whether sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy (FSHD). METHODS: Sarcomeric function was evaluated by contractile studies on demembranated single muscle fibers obtained from quadriceps muscle biopsies of 4 patients with FSHD and 4 healthy controls. The sarcomere length dependency of force was determined together with measurements of thin filament length using immunofluorescence confocal scanning laser microscopy. X-ray diffraction techniques were used to study myofilament lattice spacing. RESULTS: FSHD muscle fibers produced only 70% of active force compared to healthy controls, a reduction which was exclusive to type II muscle fibers. Changes in force were not due to changes in thin filament length or sarcomere length. Passive force was increased 5- to 12-fold in both fiber types, with increased calcium sensitivity of force generation and decreased myofilament lattice spacing, indicating compensation by the sarcomeric protein titin. CONCLUSIONS: We have demonstrated a reduction in sarcomeric force in type II FSHD muscle fibers, and suggest compensatory mechanisms through titin stiffening. Based on these findings, we propose that sarcomeric dysfunction plays a critical role in the development of muscle weakness in FSHD.
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- Faculty of Medical Sciences [90373]
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