Facioscapulohumeral Muscular Dystrophy (FSHD): Wellstone Study
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ABSTRACT:
PROVIDER: PRJNA731943 | ENA |
REPOSITORIES: ENA
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Project description:Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder linked to contractions of the D4Z4 repeat array in the subtelomeric region of chromosome 4q. By comparing genome-wide gene expression data from muscle biopsies of patients with FSHD to those of 11 other neuromuscular disorders, we intend to identify disease-specific changes which are more likely to be involved in the early stages of the disease progression. The data will help to identify pathological mechanisms involved in FSHD. Experiment Overall Design: Comparison of the profiles of FSHD to 13 other conditions for disease-specific changes. The 13 conditions are NHM (Normal healthy muscle) n=15; JDM (Juvenile dermatomyositis) n=25; HSP (Human spastic paraplegia) n=4; FSHD (facioscapulohumeral dystrophy) unaffected n=5, affected n=9; FKRP (Fukutin related protein deficiency) n=7; ED-L (Emery-Dreifuss muscular dystrophy, lamin A/C deficiency) n=4; ED-E (Emery-Dreifuss muscular dystrophy, emerin deficiency) n=4; DYSF (dysferlinopathy) n=10; DMD (Duchenne Muscular Dystrophy) n=10; CALP (Calpain-3 deficiency) n=10; BMD (Becker Muscular Dystrophy) n=5; AQM (Acute quadriplegic myopathy) n=5; ALS (Amyotrophic lateral sclerosis) n=9.
2008-06-16 | E-GEOD-9397 | biostudies-arrayexpress
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. In order to develop mRNA-based biomarkers of affected muscles, we used GeneChip Gene 1.0 ST arrays for global analysis of gene expression in muscle biopsy specimens obtained from FSHD subjects and their unaffected first degree relatives. FSHD typically affects biceps muscles more severely than deltoid muscles. To examine muscle-specific expression changes associated with FSHD while controlling for background genetic variation, we analyzed RNA extracted from both biceps and deltoids of FSHD subjects and unaffected first-degree relatives.
2012-09-19 | E-GEOD-36398 | biostudies-arrayexpress
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. In order to develop mRNA-based biomarkers of affected muscles, we used GeneChip Gene 1.0 ST arrays for global analysis of gene expression in muscle biopsy specimens obtained from FSHD subjects and their unaffected first degree relatives.
2012-09-19 | GSE36398 | GEO
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is characterized by sporadic de-repression of the transcription factor DUX4 in skeletal muscle. We employed single-cell RNA-sequencing, combined with pseudotime trajectory modeling, to study FSHD disease etiology and cellular progression in human primary myocytes. We identified a small FSHD-specific cell population in all tested patient-derived cultures and detected new genes associated with DUX4 de-repression. We furthermore generated an FSHD cellular progression model, reflecting both the early burst-like DUX4 expression as well as the downstream activation of various FSHD-associated pathways, which allowed us to correlate DUX4 expression signature dynamics with that of regulatory complexes, thereby facilitating the prioritization of epigenetic targets for DUX4 silencing.
2018-12-03 | GSE122873 | GEO
Project description:We investigated the effects of six weeks of voluntary wheel running in heterozygous B6(Cg)-Gt(ROSA)26Sortm1.1(DUX4*)Plj/J (FLExDUX4) mouse model of Facioscapulohumeral Muscular Dystrophy (FSHD) and their wild type (WT) littermates to characterize the structural/functional adaptations to voluntary wheel running and their molecular foundations using RNA sequencing
2023-12-01 | GSE233340 | GEO
Project description:Muscle biopsies taken from vastus lateralis muscle of 30 normal subjects and 19 FSHD subjects (see PubMed ID 17151338) Affymetrix U133A and U133B arrays were scanned both before (S1) and after (S2) antibody enhancement. Effects of age and sex in normal subjects reported previously under GSE362, GSE674, and GSE9676. Keywords: facioscapulohumeral dystrophy, skeletal muscle
2008-03-08 | GSE10760 | GEO
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4, a transcription factor normally silenced in skeletal muscle. Detecting DUX4 in skeletal muscle and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for other surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to analyze the protein repertoire of interstitial fluids obtained from 20 FSHD patients’ muscles in different disease stages classified by Magnetic Resonance Imaging (MRI) and controls. Serum samples from the same subjects were also analyzed. A total of 1156 proteins were identified in the microdialysates by Data Independent Acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles of interstitial fluids were able to distinguish FSHD patients from controls. Among the upregulated proteins in muscles with active disease, two innate immunity mediators (S100-A8 and A9) and Dermcidin were detected with both proteomic approaches and selectively present in the sera of FSHD patients. Structural muscle proteins were downregulated, consistent with signs of early damage, as well as proteins of the plasminogen pathway. This suggests, together with upstream inhibition in FSHD samples of myogenic factors, defective muscle regeneration and increased fibrosis already in early/active disease. Conclusions: our MRI targeted exploratory approach provided insights on pathophysiological pathways activated in early disease, confirming that inflammatory response has a prominent role, together with impaired muscle regeneration. We also identified three proteins as tissue and possibly circulating prognostic biomarkers in FSHD.
2021-09-09 | PXD021838 | Pride
Project description:Facioscapulohumeral dystrophy (FSHD) is one of the most common inherited muscular dystrophies. The causative gene remains controversial and the mechanism of pathophysiology unknown. Here we identify genes associated with germline and early stem cell development as targets of the DUX4 transcription factor, a leading candidate gene for FSHD. The genes regulated by DUX4 are reliably detected in FSHD muscle but not in controls, providing direct support for the model that misexpression of DUX4 is a causal factor for FSHD. Additionally, we show that DUX4 binds and activates LTR elements from a class of MaLR endogenous primate retrotransposons and suppresses the innate immune response to viral infection, at least in part through the activation of DEFB103, a human defensin that can inhibit muscle differentiation. These findings suggest specific mechanisms of FSHD pathology and identify candidate biomarkers for disease diagnosis and progression. Examine Dux4 full isoform binding sites in human fibroblast.
2012-01-03 | E-GEOD-33838 | biostudies-arrayexpress
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is an inherited progressive neuromuscular disorder that afflicts both children and adults regardless of gender. FSHD is caused by aberrant gain of expression of the transcription factor DUX4, which triggers a pro-apoptotic transcriptional program leading to muscle wasting. As today, no cure or therapeutic option is available to FSHD patients. Given its centrality in FSHD, blocking DUX4 expression with small molecule drugs is an attractive option. We previously showed that the long non-coding RNA DBE-T is required for aberrant DUX4 expression in FSHD. Using affinity purification followed by proteomics, we identified the chromatin remodeling protein WDR5 as a novel DBE-T interactor and a key player required for the biological activity of the lncRNA. We found that WDR5 is required for the expression of DUX4 and its targets in primary FSHD muscle cells. Moreover, targeting WDR5 rescues both cell viability and myogenic differentiation of FSHD patient cells. Notably, comparable results were obtained by pharmacological inhibition of WDR5. Importantly, WDR5 targeting was safe to healthy donor muscle cells. Our results support a pivotal role of WDR5 in the activation of DUX4 expression identifying a druggable target for an innovative therapeutic approach for FSHD.
2023-04-13 | GSE210610 | GEO
Project description:Muscle biopsies from biceps and deltoid were taken from 5 patients with FSHD, 5 asymptomatic carriers and 5 normal controls. The genome-wide expression patterns were compared using Affymetrix U133 Plus 2.0 chips. Keywords: Facioscapulohumeral, FSHD, muscular dystrophy
2009-03-04 | GSE15090 | GEO