Determining the role of sarcomeric proteins in facioscapulohumeral muscular dystrophy: a study protocol
1 Department of Neurology, Radboud university medical center, Nijmegen, The Netherlands
2 Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands
3 Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands
4 Department of Radiology, Radboud university medical center, Nijmegen, the Netherlands
5 Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
6 Department of Physiology, Radboud university medical center, Nijmegen, the Netherlands
BMC Neurology 2013, 13:144 doi:10.1186/1471-2377-13-144Published: 11 October 2013
Although muscle weakness is a hallmark of facioscapulohumeral muscular dystrophy (FSHD), the molecular mechanisms that lead to weakness in FSHD remain largely unknown. Recent studies suggest aberrant expression of genes involved in skeletal muscle development and sarcomere contractility, and activation of pathways involved in sarcomeric protein degradation. This study will investigate the contribution of sarcomeric protein dysfunction to the pathogenesis of muscle weakness in FSHD.
Evaluation of sarcomeric function using skinned single muscle fiber contractile studies and protein analysis in muscle biopsies (quadriceps femoris and tibialis anterior) from patients with FSHD and age- and gender-matched healthy controls. Patients with other forms of muscular dystrophy and inflammatory myopathy will be included as disease controls to assess whether results are due to changes specific for FSHD, or a consequence of muscle disease in general. A total of 56 participants will be included. Extensive clinical parameters will be measured using MRI, quantitative muscle studies and physical activity assessments.
This study is the first to extensively investigate muscle fiber physiology in FSHD following an earlier pilot study suggesting sarcomeric dysfunction in FSHD. The results obtained in this study will increase the understanding of the pathophysiology of muscle weakness in FSHD, and possibly identify novel targets for therapeutic intervention.