Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during childhood development

Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy caused by expansion of a CTG repeat microsatellite within DMPK. In 10-20% of individuals with DM1, symptomatic onset begins at birth; these patients are classified as congenital myotonic dystrophy (CDM). While dysregulation of RNA metabolism, specifically alternative splicing, has been linked to disease pathology in adult-onset DM1, little is known about the mechanism of CDM. Biopsies from individuals (CDM), age range 0.04-16 years, were subjected to total RNA-seq to quantify the transcriptomic dysregulation throughout pediatric development. To achieve this, they were compared against age matched pediatric controls which revealed a triphasic pattern of dysregulation not before seen observed in CDM. CDM samples were also compared to adult-onset (DM1) individuals which showcased a shared disease signature to seen in all individuals with myotonic dystrophy irrespective of disease age of onset. Overall design: Total RNA-seq on 36 skeletal muscle biopsies collected from CDM individuals, 22 adult biopsies from individuals with adult-onset DM1, 7 unaffected adult controls (AdCo), and 21 unaffected pediatric controls (PeCo). Biopsies were subjected to RNA-seq and analyzed for alternative splicing and gene expression changes. Updates: [07-28-2023] The sex characteristics was changed for GSM6056748, and the age characteristics was changed for GSM6056756, GSM6056763, GSM6056766, GSM6056768, GSM6056770, GSM6056774, and GSM6056775.