Abstract
Our objective was to investigate the potential of three microRNAs, miR-181a-5p, miR-30c-5p, and miR-206 as prognostic biomarkers for long-term follow up of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients. We analyzed the expression of three microRNAs in serum of 18 patients (DMD 13, BMD 5) and 13 controls using droplet digital PCR. Over 4 years a minimum of two and a maximum of three measurements were performed at different time points in the same patient. Correlations between microRNA serum levels, age, and functional outcome measures were analyzed. We show the individual evolution of the levels of the three microRNAs in 12 patients and also the effect of corticosteroid treatment on microRNAs expression. We measure the expression of three microRNAs in the muscle of six DMD patients and also the expression of target genes for miR-30c. We found that levels of miR-30c and miR-206 remained significantly elevated in DMD patients relative to controls over the entire study length. The introduction of the corticosteroid treatment did not significantly influence the levels of these microRNAs. We report a trend for microRNA levels to decrease with age. Moreover, miR-206 expression levels are capable to distinguish DMD from BMD patients according to ROC analysis. We found miR-30c expression decreased in the muscle of DMD patients and marked upregulation of the target genes for this microRNA. MiR-30c and miR-206 represent sensitive biomarkers for DMD, while miR-206 may have an additional value to distinguish the DMD and BMD phenotype. This may be particularly relevant to assess the effectiveness of treatments aimed at converting the DMD to the less-severe BMD like phenotype.
Highlights
Muscular dystrophies represent a heterogeneous group of disorders both from the genetic and phenotypic point of view, with muscle wasting as a common trait
Duchenne muscular dystrophy (DMD) is the most common childhood muscular dystrophy, affecting one in 5,000 male births and is caused by mutations in the X-linked DMD gene resulting in the absence or severe reduction of the dystrophin protein
A milder phenotype of Becker muscular dystrophy (BMD) arises from inframe mutations in the DMD gene resulting in a production of truncated, partially functional protein [1]
Summary
Muscular dystrophies represent a heterogeneous group of disorders both from the genetic and phenotypic point of view, with muscle wasting as a common trait. The current genetic prediction of whether a mutation will result in a DMD or BMD phenotype is the reading-frame rule (Monaco rule) [2]. There is a wide clinical spectrum of severity that does not always allow patients to be categorized as DMD or BMD, especially at early stages of the disease [5] This is important for adequately selecting patients in clinical trials, when a clear phenotype is required [6]. The role of miRNAs in the regulation of key biological processes in skeletal muscle is well-established [9] and they serve as diagnostic, prognostic biomarkers, and as molecular outcome measures in various biomedical fields [10, 11]. This can be explained by the fact that DMD patients undergo a period of normal childhood growth that may compensate for myofiber degeneration [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
