Facioscapulohumeral dystrophy: The path to consensus on pathophysiology

69Citations
Citations of this article
108Readers
Mendeley users who have this article in their library.

Abstract

Although the pathophysiology of facioscapulohumeral dystrophy (FSHD) has been controversial over the last decades, progress in recent years has led to a model that incorporates these decades of findings and is gaining general acceptance in the FSHD research community. Here we review how the contributions from many labs over many years led to an understanding of a fundamentally new mechanism of human disease. FSHD is caused by inefficient repeat-mediated epigenetic repression of the D4Z4 macrosatellite repeat array on chromosome 4, resulting in the variegated expression of the DUX4 retrogene, encoding a double-homeobox transcription factor, in skeletal muscle. Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD. Although some disagreements regarding the details of mechanisms remain in the field, the coalescing agreement on a central model of pathophysiology represents a pivot-point in FSHD research, transitioning the field from discovery-oriented studies to translational studies aimed at developing therapies based on a sound model of disease pathophysiology.

Cite

CITATION STYLE

APA

Tawil, R., van der Maarel, S. M., & Tapscott, S. J. (2014, June 10). Facioscapulohumeral dystrophy: The path to consensus on pathophysiology. Skeletal Muscle. BioMed Central Ltd. https://doi.org/10.1186/2044-5040-4-12

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free