Three non-exclusive molecular defects hypothesized to contribute to DM1 pathology are (i) decreased DMPK levels resulting from aberrant nuclear accumulation of the mutant DMPK RNA [14], [15] (ii) decreased SIX5 levels occurring as a consequence of chromatin condensation that occurs in the vicinity of the expanded CTG tract [16]–[18] and (iii) intrinsic toxicity of the expanded CUG tracts [19]. The gene discussed is SIX5; the disease is myotonic dystrophy type 1.