Two patients belonging to a consanguineous family affected by myosclerosis myopathy were examined, screened for mutations of collagen VI genes, and studied by a detailed biochemical and morphological analysis of muscle biopsy and cultured skin fibroblasts.
We demonstrated that the patients had a novel homozygous nonsense COL6A2 mutation (Q819X); the mutated messenger RNA escaped nonsense-mediated decay and was translated into a truncated alpha2(VI) chain, lacking the sole C2 domain. As a result, the mutated collagen VI was quantitatively reduced and structurally abnormal in cultured fibroblasts, did not correctly localize in the basement membrane of muscle fibers and was absent in the muscle capillary walls. Ultrastructural analysis of muscle showed an unusual combination of basement membrane thickening and duplication, along with increased number of pericytes.
In conclusion, this familial case has the characteristic features of myosclerosis myopathy and carries a homozygous COL6A2 mutation responsible for a peculiar pattern of collagen VI defects. Our study demonstrates that myosclerosis myopathy should be considered a collagen VI disorder as Ullrich congenital muscular dystrophy and Bethlem myopathy.
Merlini L, Martoni E, Grumati P, Sabatelli P, Squarzoni S, Urciuolo A, Ferlini A, Gualandi F, Bonaldo P. Autosomal recessive myosclerosis myopathy is a collagen VI disorder. Neurology. 2008. 71(16): 1245-53.
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