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Collagen VI myopathies are genetic disorders due to mutations in collagen VI A1, A2, and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy (UCMD) to the milder Bethlem myopathy (BM), which is recapitulated by collagen VI null (Col6a1−/−) mice. UCMD and BM can be inherited accordingly to both dominant and recessive models, and generally, neither the type of mutation (missense, nonsense, splicing insertion or deletion), nor the effect of the mutation allows the discrimination between two phenotypes. This suggests that the genetic background of patients may influence the mutated genes expression. To unravel the expression profiling perturbation in muscles with collagen VI myopathies we performed a deep RNA profiling in both Col6a1−/− mice and collagen VI patients. An interactome map that highlights the connection between the altered pathways, including circadian rhythms, and collagen VI pathology was built up. In order to profile both circadian and COL6 genes, we designed two novel TaqMan® low-density arrays, one covering 10 circadian genes (CLOCK, ATF5, ARNTL, EGR1, DBP, CCRN4L, FKBP5, PER1, PER2, PER3) and the other covering the full-exon composition of the three collagen VI genes. All the transcriptomic analyses revealed a profound deregulation of the circadian genes with a CLOCK upregulation in the more severe (UCMD) phenotype. We propose that CLOCK gene might be a severity biomarker for collagen6 myopathy. In addition our TaqMan assays may be used as diagnostic tools for collagen-VI related myopathy lacking molecular characterization.

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