Facioscapulohumeral dystrophy transcriptome signatures correlate with different stages of disease and are marked by different MRI biomarkers
Scientific Reports, vol. 12, pp. 1426
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.
Authors 10
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Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, Postal zone S-04-P, 2333 ZA, Leiden, The Netherlands
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Affiliation as printed
Department of Neurology, Zuyderland Medical Center, Heerlen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
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Consejo Superior de Investigaciones Científicas · Centro Nacional de Biotecnología
Affiliation as printed
Department of Systems Biology, National Center of Biotechnology (CNB-CSIC), Madrid, Spain
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Radboud University Medical Center
Affiliation as printed
Department of Radiology, Radboud University Medical Center, Nijmegen, The Netherlands
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Radboud University Medical Center
Affiliation as printed
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
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Affiliation as printed
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA
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Radboud University Nijmegen · Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, Postal zone S-04-P, 2333 ZA, Leiden, The Netherlands. S.M.van_der_Maarel@lumc.nl
Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, Postal zone S-04-P, 2333 ZA, Leiden, The Netherlands
Cited by 32 stored of 32
Cited by patents worldwide 2 (Lens.org)
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