The human myotonic dystrophy type 1 transcriptome. Homo sapiens

Myotonic dystrophy (DM) is a highly multi-systemic disorder caused by expanded CTG/CCTG repeats. Muscle weakness, myotonia, cardiac arrhythmia, and profound fatigue are common, yet exhibit extreme variability across affected individuals. Many transcriptome changes occur in DM, in particular changes in alternative splicing. Some of these changes are dependent on Muscleblind-like (MBNL) and Cugbp- and ETR3-like factors (CELF); however, numerous additional cellular pathways are perturbed, including dysregulation of transcription factors, microRNA processing, and protein signaling. To comprehensively assess transcriptome changes occurring in DM, and to evaluate the extent to which each of these pathways may contribute to disease pathogenesis, we performed RNA sequencing on a diverse panel of DM and normal biopsies/autopsies. Samples included biopsies from tibialis anterior and quadriceps, and autopsies from the heart and additional skeletal muscles across the body.