Regional and bilateral MRI and gene signatures in facioscapulohumeral dystrophy: implications for clinical trial design and mechanisms of disease progression.

Autor:	Wong CJ; Division of Human Biology, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA 98109, United States., Friedman SD; Department of Radiology, Seattle Children's Hospital, 4540 Sandpoint Way, Seattle, WA 98105, United States., Snider L; Division of Human Biology, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA 98109, United States., Bennett SR; Division of Human Biology, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA 98109, United States., Jones TI; Department of Pharmacology, University of Nevada, Reno School of Medicine, 1664 North Virginia Street, Reno, NV 89557, United States., Jones PL; Department of Pharmacology, University of Nevada, Reno School of Medicine, 1664 North Virginia Street, Reno, NV 89557, United States., Shaw DWW; Department of Radiology, Seattle Children's Hospital, 4540 Sandpoint Way, Seattle, WA 98105, United States., Blemker SS; Springbok Analytics, 100 W South St, Charlottesville, VA 22902, United States., Riem L; Springbok Analytics, 100 W South St, Charlottesville, VA 22902, United States., DuCharme O; Springbok Analytics, 100 W South St, Charlottesville, VA 22902, United States., Lemmers RJFL; Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands., van der Maarel SM; Department of Human Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands., Wang LH; Department of Neurology, University of Washington, 1959 NE Pacific St, Seattle, WA 98105, United States., Tawil R; Department of Neurology, University of Rochester Medical Center, 601 Elm St, Rochester, NY 14642, United States., Statland JM; Department of Neurology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KA 66160, United States., Tapscott SJ; Division of Human Biology, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA 98109, United States.; Department of Neurology, University of Washington, 1959 NE Pacific St, Seattle, WA 98105, United States.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2024 Apr 08; Vol. 33 (8), pp. 698-708.
DOI:	10.1093/hmg/ddae007
Abstrakt:	Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity. We further show that measurements of normalized fat content in the entire TA muscle strongly predict molecular signatures in the mid-portion of the TA, indicating that regional biopsies can accurately measure progression in the whole muscle and providing a strong basis for inclusion of MRI and molecular biomarkers in clinical trial design. An unanticipated finding was the strong correlations of molecular signatures in the bilateral comparisons, including markers of B-cells and other immune cell populations, suggesting that a systemic immune cell infiltration of skeletal muscle might have a role in disease progression. (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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