Facioscapulohumeral muscular dystrophy FSH FSHD Landouzy-Dejerine myopathy
Conditions
Interventions
None listed
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1.FSHD patients: - 18 years or older - Genetically proven FSHD or; - Clinical FSHD diagnosis and permission for genetic testing to confirm the diagnosis;2. Healthy volunteers - 18 years or older;3. Patients with an unrelated neuromuscular disease - 18 years or older - Confirmed neuromuscular disease, like Inclusion Body Myositis (IBM), Ocular pharyngeal muscular dystrophy (OPMD), Myasthenia Gravis (MG) and Lambert Eaton Myasthenic Syndrome (LEMS)
Exclusion criteria
Exclusion criteria: Healthy volunteers: In order to be eligible to participate in this study, a healthy control must not have: - A muscle disorder - A neurological disorder - A history of a urinary tract disorder interfering with urine sample acquisition
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| -To assess whether DUX4 detection in urine-derived (epithelial, stem and myogenic) cells can be used as a diagnostic marker for FSHD; -To assess whether DUX4 detection in (cells derived from) skin biopsies or buccal brush biopsies can be used as a diagnostic marker for FSHD; -To generate (induced pluripotent) stem cell and epithelial cell cultures of FSHD patients, healthy individuals, and patients with an unrelated neuromuscular disease -To identify novel biomarkers for FSHD severity in plasma from FSHD patients, healthy individuals, and patients with an unrelated neuromuscular disease. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To determine whether DUX4 and DUX4 target genes (i.e. genes regulated by DUX4) are significantly higher expressed in urine-derived stem cells of FSHD patients, thus prior to differentiation to myogenic cells, compared to controls; - To determine whether DUX4 and DUX4 target genes are significantly higher expressed in urine-derived epithelial cells of FSHD patients; - To determine whether DUX4 and DUX4 target genes are significantly higher expressed in urine-derived cells of FSHD patients compared to controls after myogenic differentiation; - To determine whether DUX4 and DUX4 target genes are significantly higher expressed in skin and epithelial cells from skin of FSHD patients compared to controls; - To determine whether DUX4 and DUX4 target genes are significantly higher expressed in cells derived from buccal brush biopsies of FSHD patients compared to control individuals; -To correlate DUX4 transcript levels in cells derived from urine, skin punch biopsies, or buccal brush biopsies to the clinical severity score and results from manual muscle testing -To correlate DUX4 transcript levels in cells derived from urine, skin punch biopsies, or buccal brush biopsies to D4Z4 sizing and D4Z4 methylation levels; - To correlate DUX4 transcript levels in cells derived from urine, skin punch biopsies, or buccal brush biopsies to cytokine levels in plasma - To assess the (epi)genetic regulation of DUX4 during development by differentiation of iPS cells into meso-, endo- and ectoderm cell types, or tissue specific cell lineages; - To perform (single cell) RNA sequencing analysis on RNA isolated from cells derived from urine, blood, skin punch biopsies, or buccal brush biopsies of FSHD patients, and compare these results with already available RNA sequencing data obtained from RNA isolated from myoblasts or muscle biopsies of FSHD patients. | — |
Countries
Netherlands
Outcome results
None listed