Differential expression of microRNAs and other small RNAs in the serum of patients with myotonic dystrophy type 1 and facioscapulohumeral muscular dystrophy type 1.

Circulating microRNAs (miRNAs) are promising non-invasive biomarkers across various diseases, including neuromuscular disorders; however, their clinical utility in myotonic dystrophy type 1 (DM1) and facioscapulohumeral muscular dystrophy type 1 (FSHD1) requires validation in diverse cohorts. We profiled serum miRNAs in patients with DM1 (n = 27), FSHD1 (n = 36), and healthy controls (n = 17) to identify differentially expressed candidates. We performed differential expression analyses, and explored the biological pathways modulated by the differentially expressed miRNAs (DEmiRNAs). In DM1, 34 DEmiRNAs were identified (log₂FC -8.97 to +4.99); hsa-miR-1306-5p, hsa-miR-483-3p, and hsa-miR-885-5p remained significant after false discovery rate (FDR) adjustment (q < 0.05). Core pathways included CREB signaling in neurons, cardiac hypertrophy signaling, and molecular mechanisms of cancer, alongside toxicity-related signatures like renal necrosis. However, these computational predictions should be interpreted with caution. In FSHD1, multiple DEmiRNAs were detected at nominal p < 0.05. However, none remained significant after FDR correction. Phenotype-miRNA analyses linked hsa-miR-208b-3p in DM1 to higher serum creatine kinase (p = 0.008). In FSHD1, hsa-miR-2277-5p correlated with later onset (p = 0.020), and detectable hsa-let-7i-3p was associated with better function. Circulating miRNAs were associated with DM1 and FSHD1 and may represent potential biomarker candidates in these disorders. In DM1, miR-1306-5p, miR-483-3p, and miR-885-5p were among the most robust candidates. Further validation studies are required to establish their clinical utility.