Abstract
The blood transcriptome was examined in relation to disease severity in type I myotonic dystrophy (DM1) patients who participated in the Observational Prolonged Trial In DM1 to Improve QoL- Standards (OPTIMISTIC) study. This sought to (a) ascertain if transcriptome changes were associated with increasing disease severity, as measured by the muscle impairment rating scale (MIRS), and (b) establish if these changes in mRNA expression and associated biological pathways were also observed in the Dystrophia Myotonica Biomarker Discovery Initiative (DMBDI) microarray dataset in blood (with equivalent MIRS/DMPK repeat length). The changes in gene expression were compared using a number of complementary pathways, gene ontology and upstream regulator analyses, which suggested that symptom severity in DM1 was linked to transcriptomic alterations in innate and adaptive immunity associated with muscle-wasting. Future studies should explore the role of immunity in DM1 in more detail to assess its relevance to DM1.
Highlights
Myotonic dystrophy type 1 (DM1) is a multi-system disease with, among others, a variety of neuromuscular and central nervous system (CNS) features
As expected, earlier onset of symptoms was associated with greater Modal CTG repeat size, as well as disease severity assessed by muscle impairment rating scale (MIRS)
In the results section we show the results of the Reactome pathway analysis (Figure 5) and the Gene Ontology (GO) term enrichment analysis for biological processes (Figure 6) on network level
Summary
Myotonic dystrophy type 1 (DM1) is a multi-system disease with, among others, a variety of neuromuscular and central nervous system (CNS) features. Patients suffer from myotonia, muscle weakness, and muscular dystrophy [1]. Cardiac abnormalities, such as conduction defects, result in a higher risk of sudden death [2]. DM1 patients often present with fatigue and symptoms related to failure of smooth muscle in internal organs [3–5]. The clinical presentation of DM1 involves physical disabilities and cognitive and emotional deficits, such as avoidance, apathy, and behavioral inflexibility [6–8]. The degree of neuromuscular impairment can be clinically assessed using the muscle impairment rating scale (MIRS) rating scale while other rating scales such as the myotonic dystrophy health index (MDHI) and DM1-Activ assess the broader phenotype [9–11]
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