Abstract
The discovery of reliable and sensitive blood biomarkers is useful for the diagnosis, monitoring and potential future therapy of diseases. Recently, microRNAs (miRNAs) have been identified in blood circulation and might have the potential to be used as biomarkers for several diseases and clinical conditions. Myotonic Dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy primarily characterized by muscle myotonia, weakness and atrophy. Previous studies have shown an association between miRNAs and DM1 in muscle tissue and, recently, in plasma. The aim of this study was to detect and assess muscle-specific miRNAs as potential biomarkers of DM1 muscle wasting, an important parameter in the disease’s natural history. Disease stable or progressive DM1 patients with muscle weakness and wasting were recruited and enrolled in the study. RNA isolated from participants’ serum was used to assess miRNA levels. Results suggest that the levels of muscle-specific miRNAs are correlated with the progression of muscle wasting and weakness observed in the DM1 patients. Specifically, miR-1, miR-133a, miR133b and miR-206 serum levels were found elevated in DM1 patients with progressive muscle wasting compared to disease stable DM1 patients. Based on these results, we propose that muscle-specific miRNAs might be useful molecular biomarkers for monitoring the progress of muscle atrophy in DM1 patients.
Highlights
Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy
In order to assess potential molecular biomarkers for monitoring muscle wasting and weakness in DM1 patients, we investigated miRNA levels that are expressed in muscle tissue; this would allow for characterisation of the progression of muscle wasting independent of other tissues that might possibly be affected in DM1 patients
Further statistical analysis was performed taking into consideration the average relative quantitation (RQ) values of the four muscle-specific miRNAs (Fig 3A)
Summary
Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy. Somatic instability is size- and age-dependent and tissue-specific causing compromised genotype-phenotype correlations [13,14,15]. It has been shown that the CTG repeat instability is caused by replication errors or processes independent of cell division such as exogenously added compounds and environmental factors [16,17,18,19,20,21] This instability leads to somatic mosaicism for the size of the CTG repeat expansion [10, 11]. The lower disease-causing threshold of repeats, there is another upper threshold beyond which an increasing repeat length makes no additional contribution toward age at onset; this implies the poor genotype-phenotype correlations observed in DM1 [28, 29]
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