ライフサイエンスコーパス: FSHD

1 FSHD has recently been hypothesized to involve abnormal

2 FSHD is a gain-of-function disease characterized by the

3 FSHD is also a chronic disease that progresses slowly ov

4 FSHD is an autosomal dominant disease linked to chromoso

5 FSHD patient myoblasts have defective myogenic different

6 FSHD patients have too few copies of a tandem 3.3-kb rep

7 FSHD region gene 1 (FRG1) is a dynamic nuclear and cytop

8 FSHD results from a unique combination of genetic and ep

9 FSHD typically results from contraction of a critical nu

10 Facioscapulohumeral dystrophy type 1 (FSHD-1) is the most common autosomal dominant form of mu

11 ncluding several genetically diagnosed adult FSHD subjects yet to show clinical manifestations of the

12 Instead, almost all FSHD patients carry deletions of an integral number of t

13 phenotypic similarities between FSHD and an FSHD-like condition caused by FAT1 mutations.

14 ges in DUX4 target gene expression are as an FSHD biomarker.

15 We furthermore generated an FSHD cellular progression model, reflecting both the ear

16 essed in the testis and causes apoptosis and FSHD when misexpressed in skeletal muscle.

17 Unfixed biopsies of control and FSHD deltoid and biceps muscles, snap-frozen at resting

18 n muscle cells and biopsies from control and FSHD individuals.

19 n between progression of differentiation and FSHD disease status.

20 ch model(s) faithfully recapitulate DUX4 and FSHD biology.

21 ified modifier locus for DUX4 expression and FSHD.

22 d experiments and validates the fidelity and FSHD relevance of multiple distinct models of DUX4 expre

23 l time points during which human healthy and FSHD myogenesis differ.

24 d that in muscle of FRG1 transgenic mice and FSHD patients, specific pre-mRNAs undergo aberrant alter

25 unique shared cytoplasm of the myotube, and FSHD cell death that depends on its activation.

26 ting from the 4q D4Z4 units in wild-type and FSHD muscle cells.

27 additional 26 subjects and predicted them as FSHD or control with 90% accuracy based on biceps and 80

28 found to be differentially expressed between FSHD and normal myoblasts.

29 criptions of phenotypic similarities between FSHD and an FSHD-like condition caused by FAT1 mutations

30 FSHD Lymphoblast score is unaltered between FSHD myoblasts/myotubes and their controls however, impl

31 Upon differentiation, both FSHD and healthy myotubes express SORBS2, suggesting tha

32 n between DME2 and the DUX4 promoter in both FSHD and unaffected primary myocytes was greatly reduced

33 Almost all patients affected by FSHD carry deletions of an integral number of tandem 3.3

34 array, these deletions are thought to cause FSHD by a position effect on other genes.

35 have been examined as candidates for causing FSHD, including the DUX4 homeobox gene in the D4Z4 repea

36 hat 54.5% of index cases display a classical FSHD phenotype with typical facial and scapular muscle w

37 a few relatives (10.0%) display a classical FSHD phenotype.

38 throughput morphological analysis describing FSHD and control myogenesis, revealing altered myogenic

39 gene repression can efficiently discriminate FSHD cells, even when no DUX4 target genes are detectabl

40 DUX4 may drive FSHD pathology via both induction of target genes and in

41 re, we choose facioscapulohumeral dystrophy (FSHD) as a model to determine whether or not targeting k

42 physiology of facioscapulohumeral dystrophy (FSHD) have led to the discovery of candidate therapeutic

43 Facioscapulohumeral dystrophy (FSHD) is associated with somatic chromatin relaxation of

44 Facioscapulohumeral dystrophy (FSHD) is caused by decreased epigenetic repression of th

45 Facioscapulohumeral dystrophy (FSHD) is caused by the mis-expression of the double-home

46 Facioscapulohumeral dystrophy (FSHD) is one of the most common inherited muscular dystr

47 Facioscapulohumeral dystrophy (FSHD; MIM158900, MIM158901) is caused by misexpression o

48 utations in Facio-Scapulo-Humeral Dystrophy (FSHD) and in an unrelated developmental disorder, Bosma

49 Facioscapulohumeral muscular dystrophy (FSHD) involves sporadic expression of DUX4, which inhibi

50 Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy characteriz

51 Facioscapulohumeral muscular dystrophy (FSHD) is a common, dominantly inherited disease caused b

52 Facioscapulohumeral muscular dystrophy (FSHD) is a muscular dystrophy caused by inefficient epig

53 Facioscapulohumeral muscular dystrophy (FSHD) is a myopathy with prevalence of 1 in 20,000.

54 Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to epig

55 Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to hypo

56 Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable skeletal myopathy.

57 Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, inherited skeletal myopathy linked

58 Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by

59 Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder linked to contra

60 Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant hereditary neuromuscular

61 Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder th

62 Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder th

63 Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant myopathy characterized by

64 Facioscapulohumeral muscular dystrophy (FSHD) is an incurable disorder linked to ectopic express

65 Facioscapulohumeral muscular dystrophy (FSHD) is associated with D4Z4 repeat contraction on huma

66 Facioscapulohumeral muscular dystrophy (FSHD) is caused by an unusual deletion with neomorphic a

67 Facioscapulohumeral muscular dystrophy (FSHD) is caused by chromatin relaxation that results in

68 ases facioscapulohumeral muscular dystrophy (FSHD) is caused by contraction of the D4Z4 repeat in the

69 Facioscapulohumeral muscular dystrophy (FSHD) is caused by deletions within the polymorphic DNA

70 Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression of the DUX4 gene;

71 Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the DUX4 t

72 Facioscapulohumeral muscular dystrophy (FSHD) is caused by the expression of DUX4 in skeletal mu

73 Facioscapulohumeral muscular dystrophy (FSHD) is characterized by sporadic de-repression of the

74 Facioscapulohumeral muscular dystrophy (FSHD) is linked to either contraction of D4Z4 repeats on

75 Facioscapulohumeral muscular dystrophy (FSHD) is linked to epigenetic dysregulation of the chrom

76 Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common types of muscular dystro

77 ying facioscapulohumeral muscular dystrophy (FSHD) much closer to the telomere in human 4q than in th

78 e in facioscapulohumeral muscular dystrophy (FSHD) pathogenesis, although the molecular mechanisms re

79 Facioscapulohumeral muscular dystrophy (FSHD) results from expression of the full-length double

80 with facioscapulohumeral muscular dystrophy (FSHD) type 2.

81 uses facioscapulohumeral muscular dystrophy (FSHD) when occurring on a specific haplotype of 4qter (4

82 d in facioscapulohumeral muscular dystrophy (FSHD), a dominant disease thought to involve local patho

83 ng facio-scapulo-humeral muscular dystrophy (FSHD), acute lymphoblastic leukemia, and sarcomas.

84 tudy facioscapulohumeral muscular dystrophy (FSHD), simultaneously recording the haplotype, copy numb

85 Facioscapulohumeral muscular dystrophy (FSHD), the most prevalent myopathy afflicting both child

86 for facioscapulohumeral muscular dystrophy (FSHD), whereby de-repression of the D4Z4 macrosatellite

87 uses facioscapulohumeral muscular dystrophy (FSHD).

88 s of Facioscapulohumeral muscular dystrophy (FSHD).

89 uses facioscapulohumeral muscular dystrophy (FSHD).

90 s in facioscapulohumeral muscular dystrophy (FSHD).

91 to fascioscapulohumeral muscular dystrophy (FSHD).

92 uses facioscapulohumeral muscular dystrophy (FSHD).

93 Facioscapulohumeral muscular dystrophy (FSHD: MIM#158900) is a common myopathy with marked but l

94 ray (facioscapulohumeral muscular dystrophy, FSHD) despite sequence conservation in repeat units thro

95 ffects of expressing variable levels of each FSHD candidate gene on myoblasts.

96 t mice with disrupted Fat1 functions exhibit FSHD-like phenotypes, we have investigated the expressio

97 estions as to what is the true aetiology for FSHD, the epigenetic events associated with the disease

98 here remains no transcriptomic biomarker for FSHD progression.

99 expression is an inconsistent biomarker for FSHD skeletal muscle biopsies, displaying efficacy only

100 Biomarkers for FSHD have focused on DUX4 target gene expression.

101 misexpression of DUX4 is a causal factor for FSHD.

102 ription factor, a leading candidate gene for FSHD.

103 We propose a hypothesis for FSHD in which DUX4 expression interferes with Pax7 in sa

104 ion in FSHD muscle, and has implications for FSHD pathogenesis.

105 We propose a revised model for FSHD in which FAT1 levels might play a role in determini

106 To identify the gene responsible for FSHD pathogenesis, we generated transgenic mice selectiv

107 s siRNAs could be a therapeutic strategy for FSHD.

108 4-fl expression per se is not sufficient for FSHD muscle pathology and indicate that quantitative mod

109 ral other mechanisms have been suggested for FSHD pathophysiology and it remains unknown whether DUX4

110 xploited for development of therapeutics for FSHD.

111 on has been proposed as the main trigger for FSHD.

112 of size of D4Z4 alleles is commonly used for FSHD diagnosis.

113 ogenic cells and muscle tissues derived from FSHD affected subjects, including several genetically di

114 arker of 237 up-regulated genes derived from FSHD lymphoblastoid cell lines is elevated in FSHD muscl

115 re, we have utilized myoblasts isolated from FSHD patients (FSHD myoblasts) to investigate the effect

116 Investigation of heterozygous FSHD myoblasts demonstrated no significant displacement

117 DUX4 in myoblasts, and differentiated human FSHD myocytes expressing endogenous DUX4-and show that t

118 transcriptional profiles of MRI-guided human FSHD muscle biopsies.

119 uscle as well the myopathology seen in human FSHD disease.

120 t recapitulates the phenotypes seen in human FSHD patients.

121 al model that mirrors the pathology in human FSHD.

122 low-level, sporadic DUX4 expression of human FSHD muscle as well the myopathology seen in human FSHD

123 n or genistein, each rescued the hypotrophic FSHD myotube phenotype.

124 e results support the use of MRI to identify FSHD muscles most likely to have active disease and high

125 facilitate pairwise comparisons to identify FSHD-specific differences and are expected to create new

126 Here, we show that EBV-immortalized FSHD lymphoblastoid cell lines express DUX4 and both ear

127 rs at low frequency but in high abundance in FSHD myotube nuclei.

128 us studies showing p53 pathway activation in FSHD muscles.

129 es of RNA expression and disease activity in FSHD muscle biopsies.

130 both DUX4-expressing murine myoblasts and in FSHD patient-derived myoblasts.

131 e majority of the gene expression changes in FSHD skeletal muscle together with an immune cell infilt

132 stress sensitivity and epigenetic changes in FSHD.

133 rity of the sarcolemma may be compromised in FSHD.

134 scription when epigenetically derepressed in FSHD, resulting in the pathological misexpression of DUX

135 However, DUX4 is difficult to detect in FSHD muscle biopsies and it is debatable how robust chan

136 , DUX4 is notoriously difficult to detect in FSHD muscle cells, while DUX4 target gene expression is

137 ith short telomeres, while not detectable in FSHD myoblasts with long telomeres or in healthy myoblas

138 s regulated by DUX4 are reliably detected in FSHD muscle but not in controls, providing direct suppor

139 protein, DUX4-FL, which has been detected in FSHD, but not in unaffected control myogenic cells and m

140 ier that underlie sex-related differences in FSHD by protecting against myoblast differentiation impa

141 ly based on endogenous expression of DUX4 in FSHD cells or by mis-expression of DUX4 in control human

142 the current hypothesis for a role of DUX4 in FSHD pathogenesis.

143 al therapeutic approach to silencing DUX4 in FSHD.

144 This myogenesis biomarker was elevated in FSHD and control healthy myotubes compared to their myob

145 SHD lymphoblastoid cell lines is elevated in FSHD muscle biopsies compared to controls.

146 previous studies showed DUX4 was elevated in FSHD patient muscles, our data support the hypothesis th

147 generative response is regularly elicited in FSHD muscle, prompting this study.

148 SORBS2 is expressed in FSHD myoblasts with short telomeres, while not detectabl

149 R-133b, and miR-206 were highly expressed in FSHD myoblasts, which nonetheless did not prematurely en

150 enes or pathways differentially expressed in FSHD patients, or associated with disease severity.

151 We first analyzed FAT1 expression in FSHD adult muscles and determined whether FAT1 expressio

152 , and its contribution to gene expression in FSHD muscle biopsies.

153 nsistent with 'bursts' of DUX4 expression in FSHD muscle, and has implications for FSHD pathogenesis.

154 s in mitochondrial structure and function in FSHD muscle, and sensitivity of FSHD cells to oxidative

155 ted the expression of the human FAT1 gene in FSHD.

156 rts a role for the D4Z4-encoded DUX4 gene in FSHD.

157 pression suggesting potential role of GQs in FSHD pathogenesis.

158 e aberrant expression has been implicated in FSHD pathogenesis.

159 A through a double-negative feedback loop in FSHD muscle cells.

160 However, DUX4 expression is extremely low in FSHD muscle, and there is no DUX4 animal model that mirr

161 muscle biopsies, FAT1 expression is lower in FSHD muscles compared to control muscles.

162 mice for modeling pathological mechanisms in FSHD and highlighting the importance FAPs in this diseas

163 hanisms driving such disrupted myogenesis in FSHD are poorly understood.

164 h resolution that occur during myogenesis in FSHD ex vivo, identifying suppression of the PGC1alpha-E

165 m in controls to values as high as 550 nm in FSHD.

166 , can recapitulate the phenotype observed in FSHD patients in a vertebrate model.

167 Immune gene misregulation occurs in FSHD muscle, with DUX4 target genes enriched for those a

168 target gene expression was detected only in FSHD-affected muscles and not in control muscles.

169 entified in this region are overexpressed in FSHD myoblasts, including the double homeobox genes DUX4

170 ion leads to inappropriate overexpression in FSHD skeletal muscle of 4q35 genes located upstream of D

171 investigation of DUX4 and the p53 pathway in FSHD pathogenesis.

172 that up-regulation of both DUX4 and PITX1 in FSHD muscles may play critical roles in the molecular me

173 As targeted therapies are now possible in FSHD, a better understanding of the relationship between

174 One site was seen preferentially in FSHD myoblasts.

175 Muscle regeneration in FSHD was correlated with the pathological hallmarks of f

176 In summary, PAX7 target gene repression in FSHD correlates with disease severity, independently of

177 Loss of D4Z4 repression in FSHD is observed as hypomethylation of the array accompa

178 In summary, the regenerative response in FSHD muscle biopsies correlates with the severity of pat

179 the discovery of DUX4 and its causal role in FSHD, most trials were untargeted with limited results.

180 ificantly up-regulated, suggesting a role in FSHD.

181 some of the structures at the sarcolemma in FSHD samples were misaligned with respect to the underly

182 nt for most of the molecular changes seen in FSHD.

183 The relative chromatin DNaseI sensitivity in FSHD and control myoblasts and lymphoblasts was as follo

184 pression is the major molecular signature in FSHD muscle together with a gene expression signature co

185 e mapped DNaseI-hypersensitive (DH) sites in FSHD and control myoblasts.

186 Subsequent in vitro study in FSHD patient myoblasts indicated that berberine treatmen

187 s could be accounted for by the fact that in FSHD myoblasts, functionally important target genes, inc

188 egulated by TPE-OLD-dependent variegation in FSHD myoblasts.

189 ted in muscle biopsies from most independent FSHD, DM2 or Duchenne muscular dystrophy (DMD) studies c

190 developmental stages is sufficient to induce FSHD-like phenotypes in later adulthood.

191 n, one unaffected individual without a known FSHD-causing mutation showed the expression of DUX4 targ

192 a sibling with FSHD and also without a known FSHD-causing mutation, suggesting the presence of an uni

193 In leading FSHD pathogenesis models, D4Z4 contractions are proposed

194 effective therapeutic strategy for at least FSHD.

195 GHD and LH/FSHD were not treated in 99.7% and 78.5% of affected ind

196 evelopment over time is noted for GHD and LH/FSHD with possible associations between nontreatment of

197 t prevalence was 46.5% for GHD, 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD, and the cumulativ

198 le mass and exercise tolerance; untreated LH/FSHD was associated with hypertension, dyslipidemia, low

199 hite race was significant associated with LH/FSHD and TSHD.

200 GHD; doses >/= 22 Gy were associated with LH/FSHD; and doses >/= 30 Gy were associated with TSHD and

201 besity were significantly associated with LH/FSHD; white race was significant associated with LH/FSHD

202 e sequencing analysis indicated that in most FSHD myocytes, both enhancers are associated with nucleo

203 rtantly all relatives of index cases with no FSHD phenotype were healthy carriers.

204 data permitted identification of many novel FSHD pathomechanisms undetectable by previous approaches

205 icism for D4Z4 repeat contraction in de novo FSHD, we have established a clonal myogenic cell model f

206 one or more regenerating myofibres in 76% of FSHD muscle biopsies from quadriceps and 91% from tibial

207 multaneous miRNome/transcriptome analysis of FSHD and control primary myoblasts.

208 esenting a significantly better biomarker of FSHD cells than DUX4 target gene expression.

209 ression is a uniquely sensitive biomarker of FSHD progression and pathology, valid over a 1 year time

210 t gene repression is a superior biomarker of FSHD status compared with DUX4 target gene expression.

211 is a leading candidate gene as causative of FSHD.

212 n and late onset phenotype characteristic of FSHD patients.

213 criptomics and histopathology on a cohort of FSHD patients with 1-year follow-up.

214 bes obtained from two independent cohorts of FSHD patients.

215 ssion associates with clinical correlates of FSHD disease activity, measured by MRI and histopatholog

216 amily genetic background are determinants of FSHD muscle disease progression.

217 possible to perform conclusive diagnosis of FSHD, but all these cases need further studies for a pro

218 increased engraftment and differentiation of FSHD myoblasts in regenerating mouse muscle.

219 omarker was a robust binary discriminator of FSHD, DM2 and DMD from controls.

220 Here, we explore the evolution of FSHD clinical trials from nonspecific anabolic or anti-i

221 combined advances across multiple facets of FSHD research, the field is now poised to accelerate the

222 PAX7 target gene repression is a hallmark of FSHD skeletal muscle.

223 PAX7 target gene repression is a hallmark of FSHD that should be considered in the investigation of F

224 ession of PAX7 target genes is a hallmark of FSHD, and that it is as major a signature of FSHD muscle

225 on that is considered a clinical hallmark of FSHD.

226 on, dystrophic muscle presented hallmarks of FSHD histopathology, including muscle degeneration, capi

227 counteract the differentiation impairment of FSHD myoblasts without affecting cell proliferation or s

228 should be considered in the investigation of FSHD pathology and therapy.

229 ls may contribute the molecular landscape of FSHD muscle biopsies.

230 s a significant biomarker in the majority of FSHD cells that are DUX4 target gene negative, and on wh

231 rom year 1 to year 2 and is thus a marker of FSHD progression over 1 year.

232 r PAX7 target gene repression as a marker of FSHD progression.

233 hese findings suggest specific mechanisms of FSHD pathology and identify candidate biomarkers for dis

234 Animal models of FSHD are hindered by incomplete knowledge regarding the

235 ata generated from three different models of FSHD-lentiviral-based DUX4 expression in myoblasts, doxy

236 s derived from biceps and deltoid muscles of FSHD affected subjects and their unaffected first-degree

237 inct muscles obtained from a large number of FSHD subjects and their unaffected first-degree relative

238 ng early development results in the onset of FSHD-like phenotypes in adulthood, even when DUX4 is no

239 of DUX4 misexpression in the pathogenesis of FSHD and should be factored into the design of future th

240 lopment is important for the pathogenesis of FSHD.

241 To better understand the pathophysiology of FSHD and develop mRNA-based biomarkers of affected muscl

242 Our results show that the pathophysiology of FSHD includes novel changes in the organization of the s

243 The pathophysiology of FSHD is unknown and, as a result, there is currently no

244 en developed to study the pathophysiology of FSHD, frequently based on endogenous expression of DUX4

245 re new candidates for the pathophysiology of FSHD.

246 for understanding the reduced penetrance of FSHD within families.

247 the D4Z4 repeat and increased penetrance of FSHD.

248 function in FSHD muscle, and sensitivity of FSHD cells to oxidative stress.

249 FSHD, and that it is as major a signature of FSHD muscle as DUX4 target gene expression.

250 es not account for the tissue specificity of FSHD pathology, which requires stable expression of an a

251 muscles that are affected at early stages of FSHD progression than in muscles that are affected later

252 itate mechanistic and therapeutic studies of FSHD.

253 DUX4 protein is present in a small subset of FSHD muscle cells, making its detection and analysis of

254 r the complexity and age-related symptoms of FSHD.

255 tyrosine kinase inhibitors for treatment of FSHD.

256 el therapeutic strategy for the treatment of FSHD.

257 modeling thus holds valuable information on FSHD disease etiology and progression that can potential

258 studies, and validated by RNA-sequencing on FSHD patient-derived myoblasts.

259 he D4Z4 repeat array, being either normal or FSHD sized.

260 et gene repression increases in these paired FSHD samples from year 1 to year 2 and is thus a marker

261 lized myoblasts isolated from FSHD patients (FSHD myoblasts) to investigate the effect of estrogens o

262 ng the likely clinical relevance of proposed FSHD biomarkers.

263 ear follow-up evaluations identified several FSHD subgroups based on gene expression, as well as a se

264 However, even in cases of severe FSHD the presence of DUX4 is barely detectable.

265 his is shown using meta-analysis of over six FSHD muscle biopsy gene expression studies, and validate

266 We identified a small FSHD-specific cell population in all tested patient-deri

267 ith pseudotime trajectory modeling, to study FSHD disease etiology and cellular progression in human

268 We find that FSHD and BAMS patient's cells carrying SMCHD1 mutations

269 Recent studies have proposed that FSHD pathology is caused by the misexpression of the DUX

270 Collectively, our results suggest that FSHD results from inappropriate overexpression of FRG1 i

271 The FSHD Lymphoblast score is unaltered between FSHD myoblas

272 cis; however which candidate gene causes the FSHD phenotype, and through what mechanism, is unknown.

273 ssification hold the potential to enrich the FSHD clinical trial toolbox.

274 Our results provide a resource for the FSHD community and illustrate the importance of post-tra

275 Identifying the FSHD transcriptome in individual cells and unraveling th

276 Indeed, the FSHD Lymphoblast score correlates with the early stages

277 ates re-examination of current models of the FSHD disease mechanism.

278 However, there lacks an assessment of the FSHD immune cell transcriptome, and its contribution to

279 expression recapitulates key features of the FSHD molecular phenotype, including repression of MyoD a

280 control genes-that distinguished all of the FSHD samples from the controls.

281 from genetically unaffected relatives of the FSHD subjects, although at a significantly lower frequen

282 ish a basis for animal models recreating the FSHD transcriptome.

283 Thus, FSHD lymphoblastoid cell lines express DUX4 and early an

284 ve functional significance, possibly also to FSHD, despite their paucity of known genes.

285 onstraints that link short 4q D4Z4 arrays to FSHD and make long ones phenotypically neutral.

286 enic differentiation and could contribute to FSHD pathology by preventing satellite cell-mediated rep

287 esis that DUX4 overexpression contributes to FSHD development.

288 unraveling the cascade of events leading to FSHD development may therefore provide important insight

289 expression of DUX4 in somatic cells leads to FSHD.

290 ough no gene has been conclusively linked to FSHD development, recent evidence supports a role for th

291 tions on the pathogenic mechanism underlying FSHD.

292 uently, the pathogenic mechanisms underlying FSHD have been difficult to discern.

293 well as the downstream activation of various FSHD-associated pathways, which allowed us to correlate

294 xpression biomarkers are not associated with FSHD progression over 1 year.

295 muscles of iDUX4pA-HSA mice and humans with FSHD, solidifying the value of chronic rare DUX4 express

296 the lower extremities in 36 individuals with FSHD, followed by needle muscle biopsies in safely acces

297 n data from muscle biopsies of patients with FSHD to those of 11 other neuromuscular disorders, paire

298 d specifically up-regulated in patients with FSHD.

299 This individual has a sibling with FSHD and also without a known FSHD-causing mutation, sug

300 und in healthy individuals, in subjects with FSHD or affected by other myopathies.