The two DNA-binding homeodomains of DUX4 show homology to the single homeodomain of the myogenic master regulator PAX7,23 suggesting overlap in DUX4 and PAX7 function.18,24 We have demonstrated that PAX7 target gene repression hallmarks FSHD muscle regardless of inflammatory state, associating with histological and MRI measures of pathological severity.17-19 Our PAX7 target gene repression biomarker has been independently verified.20,22 Importantly, PAX7 target gene repression progresses in muscle biopsies from the same FSHD patient 1 year apart, associating with disease duration.25 This evidence concerns the gene DUX4 and facioscapulohumeral muscular dystrophy.