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Facioscapulohumeral dystrophy transcriptome signatures correlate with different stages of disease and are marked by different MRI biomarkers
- Source :
- Scientific Reports, 12, 1, Scientific Reports, 12(1). NATURE PORTFOLIO, Scientific Reports, Scientific Reports, Vol 12, Iss 1, Pp 1-18 (2022), Scientific Reports, 12
- Publication Year :
- 2022
- Publisher :
- NATURE PORTFOLIO, 2022.
-
Abstract
- With several therapeutic strategies for facioscapulohumeral muscular dystrophy (FSHD) entering clinical testing, outcome measures are becoming increasingly important. Considering the spatiotemporal nature of FSHD disease activity, clinical trials would benefit from non-invasive imaging-based biomarkers that can predict FSHD-associated transcriptome changes. This study investigated two FSHD-associated transcriptome signatures (DUX4 and PAX7 signatures) in FSHD skeletal muscle biopsies, and tested their correlation with a variety of disease-associated factors, including Ricci clinical severity score, disease duration, D4Z4 repeat size, muscle pathology scorings and functional outcome measures. It establishes that DUX4 and PAX7 signatures both show a sporadic expression pattern in FSHD-affected biopsies, possibly marking different stages of disease. This study analyzed two imaging-based biomarkers—Turbo Inversion Recovery Magnitude (TIRM) hyperintensity and fat fraction—and provides insights into their predictive power as non-invasive biomarkers for FSHD signature detection in clinical trials. Further insights in the heterogeneity of—and correlation between—imaging biomarkers and molecular biomarkers, as provided in this study, will provide important guidance to clinical trial design in FSHD. Finally, this study investigated the role of infiltrating non-muscle cell types in FSHD signature expression and detected potential distinct roles for two fibro-adipogenic progenitor subtypes in FSHD.
- Subjects :
- Male
musculoskeletal diseases
congenital, hereditary, and neonatal diseases and abnormalities
Science
Biopsy
Severity of Illness Index
Article
All institutes and research themes of the Radboud University Medical Center
Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15]
Humans
Muscle, Skeletal
Homeodomain Proteins
Multidisciplinary
Gene Expression Profiling
Stem Cells
PAX7 Transcription Factor
Middle Aged
Neuromuscular disease
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
Magnetic Resonance Imaging
Muscular Dystrophy, Facioscapulohumeral
nervous system diseases
Gene Expression Regulation
Case-Control Studies
Medicine
Female
Transcriptome
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, 12, 1, Scientific Reports, 12(1). NATURE PORTFOLIO, Scientific Reports, Scientific Reports, Vol 12, Iss 1, Pp 1-18 (2022), Scientific Reports, 12
- Accession number :
- edsair.doi.dedup.....f9fca72d8f4e4aaab123de050e5184b0