Brittney A Otero, Kiril Poukalov, Ryan P Hildebrandt, Charles A Thornton, Kenji Jinnai, Harutoshi Fujimura, Takashi Kimura, Katharine A Hagerman, Jacinda B Sampson, John W Day, Eric T Wang
Myotonic dystrophy (DM) is caused by expanded CTG/CCTG repeats, causing symptoms in skeletal muscle, heart, and central nervous system (CNS). CNS issues are debilitating and include hypersomnolence, executive dysfunction, white matter atrophy, and neurofibrillary tangles. Here, we generate RNA-seq transcriptomes from DM and unaffected frontal cortex and identify 130 high-confidence splicing changes, most occurring only in cortex, not skeletal muscle or heart. Mis-spliced exons occur in neurotransmitter receptors, ion channels, and synaptic scaffolds, and GRIP1 mis-splicing modulates kinesin association...
January 19, 2021: Cell Reports