Pluto Bioinformatics

GSE115650: MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD

Bulk RNA sequencing

Facioscapulohumeral muscular dystrophy (FSHD) is a common, dominantly inherited disease caused by the epigenetic de-repression of the DUX4 gene, a transcription factor normally repressed in somatic cells. As targeted therapies are now possible in FSHD, a better understanding of the relationship between DUX4 activity, muscle pathology and muscle MRI changes are crucial both to understand disease mechanisms and for the design of future clinical trials. Here, we performed MRIs of the lower extremities in 36 individuals with FSHD, followed by needle muscle biopsies in safely accessible muscles. We examined the correlation between MRI characteristics, muscle pathology, and expression of DUX4 target genes. Results show that the presence of elevated MRI STIR signal has substantial predictive value in identifying muscles with active disease and DUX4 target gene expression. In addition, DUX4 target gene expression was detected only in FSHD-affected muscles and not in control muscles, and higher levels of DUX4 target expression was associated with more advanced muscle pathology. These results support the use of MRI to identify FSHD muscles with active disease as measured by histopathology and DUX4 target gene expression and might be useful for the design of studies of disease progression and response to intervention. SOURCE: Stephen Tapscott ( - Tapscott Fred Hutchison Cancer Research Center

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