The discovery of the DNA methylation episignature for Duchenne muscular dystrophy

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder characterized by progressive muscle weakness due to loss of function mutations in the dystrophin gene. Variation in clinical presentation, the rate of disease progression, and treatment responsiveness have been observed amongst DMD patients, suggesting that factors beyond the loss of dystrophin may contribute to DMD pathophysiology. Epigenetic mechanisms are becoming recognized as important factors implicated in the etiology and progression of various diseases. A growing number of genetic syndromes have been associated with unique genomic DNA methylation patterns (called "episignatures") that can be used for diagnostic testing and as disease biomarkers. To further investigate DMD pathophysiology, we assessed the genome-wide DNA methylation profiles of peripheral blood from 36 patients with DMD using the combination of Illumina Infinium Methylation EPIC bead chip array and EpiSign technology. We identified a unique episignature for DMD that whose specificity was confirmed in relation other neurodevelopmental disorders with known episignatures. By modeling the DMD episignature, we developed a new DMD episignature biomarker and provided novel insights into the molecular pathogenesis of this disorder, which have the potential to advance more effective, personalized approaches to DMD care.