
Myotonic Dystrophy (DM) is a multisystemic disorder and the second most common form of muscular dystrophy. Major features of the disease include myotonia, muscle wasting, insulin resistance, cardiac conduction defects, cataracts, cognitive dysfunction and mental retardation in the most severe congenital form of the disease. Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in the DMPK gene. The predominant mechanism of pathogenesis is a toxic gain of function of CUG repeats containing RNA transcribed from the expanded allele. The molecular mechanisms by which the RNA containing expanded repeats produce pathogenic effects include: sequestration of muscleblind-like 1 (MBNL1) protein and up-regulation of CUG binding protein 1 (CUGBP1). Cardiac manifestations occur in more than 80% of individuals with DM1. Conduction abnormalities often progress to life-threatening arrhythmias such that sudden death due to cardiac causes occurs in up to 30% of individuals with DM1. Previous studies have shown that cardiovascular disease comprised the second most common cause of mortality. In this study, Misha Koshelev and colleagues aimed to determine whether CUGBP1 overexpression in cardiac tissue is sufficient to reproduce the cardiac phenotype of DM1.