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MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD.
Wang, Leo H; Friedman, Seth D; Shaw, Dennis; Snider, Lauren; Wong, Chao-Jen; Budech, Chris B; Poliachik, Sandra L; Gove, Nancy E; Lewis, Leann M; Campbell, Amy E; Lemmers, Richard J F L; Maarel, Silvère M; Tapscott, Stephen J; Tawil, Rabi N.
Afiliación
  • Wang LH; Department of Neurology, University of Washington, Seattle, WA, USA.
  • Friedman SD; Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
  • Shaw D; Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
  • Snider L; Department of Radiology, University of Washington, Seattle, WA, USA.
  • Wong CJ; Human Biology Division, Fred Hutchinson Research Center, Seattle, WA, USA.
  • Budech CB; Human Biology Division, Fred Hutchinson Research Center, Seattle, WA, USA.
  • Poliachik SL; Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
  • Gove NE; Department of Radiology, Seattle Children's Hospital, Seattle, WA, USA.
  • Lewis LM; Center for Clinical and Translational Research, Seattle Children's Hospital, Seattle, WA, USA.
  • Campbell AE; Neuromuscular Unit, Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
  • Lemmers RJFL; Human Biology Division, Fred Hutchinson Research Center, Seattle, WA, USA.
  • Maarel SM; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
  • Tapscott SJ; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
  • Tawil RN; Human Biology Division, Fred Hutchinson Research Center, Seattle, WA, USA.
Hum Mol Genet ; 28(3): 476-486, 2019 02 01.
Article en En | MEDLINE | ID: mdl-30312408
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 skeletal muscle. As targeted therapies are now possible in FSHD, a better understanding of the relationship between DUX4 activity, muscle pathology and muscle magnetic resonance imaging (MRI) changes is 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 short tau inversion recovery signal has substantial predictive value in identifying muscles with active disease as determined by histopathology and DUX4 target gene expression. In addition, DUX4 target gene expression was detected only in FSHD-affected muscles and not in control muscles. These results support the use of MRI to identify FSHD muscles most likely to have active disease and higher levels of DUX4 target gene expression and might be useful in early phase therapeutic trials to demonstrate target engagement in therapies aiming to suppress DUX4 expression.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Músculo Esquelético / Proteínas de Homeodominio / Distrofia Muscular Facioescapulohumeral Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Músculo Esquelético / Proteínas de Homeodominio / Distrofia Muscular Facioescapulohumeral Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos