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© 2008 American Academy of Neurology Autosomal recessive myosclerosis myopathy is a collagen VI disorderFrom the Department of Experimental and Diagnostic Medicine (L.M., E.M., A.F., F.G.), Section of Medical Genetics, University of Ferrara; Department of Histology, Microbiology and Medical Biotechnologies (P.G., A.U., P.B.), University of Padova; and IGM-CNR (P.S., S.S.), Unit of Bologna c/o IOR, Italy. Address correspondence and reprint requests to Dr. Paolo Bonaldo, Dipartimento di Istologia, Microbiologia e Biotecnologie Mediche, Viale Giuseppe Colombo 3, I-35121 Padova, Italy bonaldo{at}bio.unipd.it Objective: To determine the clinical and molecular features of a new phenotype related to collagen VI myopathies. Methods: We examined two patients belonging to a consanguineous family affected by myosclerosis myopathy, screened for mutations of collagen VI genes, and performed a detailed biochemical and morphologic analysis of the muscle biopsy and cultured fibroblasts.
Results: The patients had a novel homozygous nonsense COL6A2 mutation (Q819X); the mutated messenger RNA escaped nonsense-mediated decay and was translated into a truncated Conclusions: 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 allelic to Ullrich congenital muscular dystrophy and Bethlem myopathy.
Abbreviations: BM = Bethlem myopathy; cDNA = complementary DNA; ECM = extracellular matrix; mRNA = messenger RNA; NMD = nonsense-mediated decay; UCMD = Ullrich congenital muscular dystrophy.
Supplemental data at www.neurology.org *These authors contributed equally. Supported by grants from the Italian Telethon Foundation (GGP04113 and GUP07004), the Italian Ministry for University (PRIN 2005), and the Italian Health Ministry (RF 2005). Disclosure: The authors report no disclosures. Received March 20, 2008. Accepted in final form July 7, 2008. This article has been cited by other articles:
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2(VI) chain, lacking the sole C2 domain. The truncated chain associated with the other two chains, giving rise to secreted collagen VI. Monomers containing the truncated chain were assembled into dimers, but tetramers were almost absent; secreted collagen VI was quantitatively reduced and structurally abnormal in cultured fibroblasts. Mutated collagen did not correctly localize in the basement membrane of muscle fibers and was absent in the capillary wall. Ultrastructural analysis of muscle showed an unusual combination of basement membrane thickening and duplication, and increased number of pericytes. 
