Introduction

FSHD is caused by inefficient epigenetic repression of the DUX4 gene. DUX4 encodes a transcription factor whose expression is normally restricted to early embryonic development. Gain-of-function of DUX4 in muscle tissue of FSHD patients initiates a transcription cascade ultimately resulting in overt muscle pathology. Repressing the expression of DUX4 offers a valid approach for therapeutic intervention. Given the complex regulatory mechanisms involved in DUX4 repression, the use of primary patientderived myotubes is warranted for optimal translatability.