Transcriptomic Profile of Skeletal Muscle Biopsies from Duchenne and Becker Muscular Dystrophy Patients

The complexity of RNA metabolism has become crucial in neuromuscular diseases, especially for Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD). DMD is associated with mutations in Dystrophin gene that disrupt the protein reading frame causing premature stop codons. In contrast, patients with BMD usually have in-frame deletions that maintain the correct reading frame. Our goal is to search for possible pathways that differs between the two diseases, in which DMD develop a severe phenotype compared to BMD. Here we aimed to evaluate the transcriptomic profile in muscle biopsy of DMD and BMD patients. We collected RNA obtained from muscle biopsy of pediatric DMD patients (n=12) and BMD patients (n=6). Through RNA sequencing, the differentially expressed (DE) genes of DMD patients versus BMD patients were analyzed. Through principal component analysis (PCA), we were able to identify a clear difference between the two groups based on gene expression pattern. DMD patients compared to BMD patients showed a particular activation of genes involved in collagen synthesis, extracellular matrix organization, and oncostatin M-dependent pathways, which plays an important role in the fibrosis process. This suggests that a more severe phenotype in DMD than BMD patients may be due to greater deregulation of these pathways, reflecting the clinical picture of patients observed. Furthermore mRNAs expression levels evaluated by RT-qPCR confirmed RNA-seq data. Enrichment pathways analysis revealed the strong alteration in collagen synthesis and extracellular matrix organization, suggesting different severity degree in the establishment of fibrotic processes. All the collagen genes validated by RT-qPCR were strongly upregulated in DMD patients. This study provides preliminary insights into the difference in gene expression between the two groups and lays the basis for the identification of possible mechanism that differentiate between the two diseases.