Collagen VI-related myopathies are a group of disorders that cause muscle weakness and joint contractures with significant variability in disease severity among patients. Here we report the clinical and genetic characteristics of 13 Chinese patients. Detailed histological, radiological and muscle transcriptomic evaluations were also conducted for selected representative patients. Across the cohort, fifteen putative disease causal variants were identified in three genes encoding collagen VI subunits, COL6A1 (n=6), COL6A2 (n=5), and COL6A3 (n=4). Most of these variants (12/15, 80%) were dominant negative and occurred at the triple helical domain. The rest (3/15, 20%) were located at the C-terminus. Two previously unreported variants, an in-frame mutation (COL6A1:c.1084_1092del) and a missense mutation (COL6A2:c.811G>C), were also noted. The transcriptome data from the muscle biopsies of two patients in the study with dominant negative mutations [COL6A2:c.811G>C and COL6A1:c.930+189C>T] supports the accepted aetiology of Collagen VI myopathy as dysfunction of the extracellular matrix. It also suggests there are perturbations to skeletal muscle differentiation and skeletal system development. It should be noted that although the phenotypes of patients can be mostly explained by the position and dominant-negative effect of the variants, exceptions and variability still exist and have to be reckoned with. This study provides valuable data explaining the varying severity of phenotypes among ethnically Chinese patients.
Keywords: Bethlem myopathy; COL6A1; COL6A2; COL6A3; Collagen-related myopathies; Ullrich congenital muscular dystrophy.
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