Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy

Saskia Lassche, Ger J.M. Stienen, Tom C. Irving, Silvère M. Van Der Maarel, Nicol C. Voermans, George W. Padberg, Henk Granzier, Baziel G.M. Van Engelen, Coen A.C. Ottenheijm

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)733-737
Number of pages5
JournalNeurology
Volume80
Issue number8
DOIs
StatePublished - Feb 19 2013

ASJC Scopus subject areas

  • Clinical Neurology

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    Lassche, S., Stienen, G. J. M., Irving, T. C., Van Der Maarel, S. M., Voermans, N. C., Padberg, G. W., Granzier, H., Van Engelen, B. G. M., & Ottenheijm, C. A. C. (2013). Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy. Neurology, 80(8), 733-737. https://doi.org/10.1212/WNL.0b013e318282513b