ColVI-myopathies: where do we stand, where do we go?

Abstract : ABSTRACT: Collagen VI-myopathies, caused by mutations in the genes encoding collagen type VI (ColVI), represent a clinical continuum with Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) at each end of the spectrum, and less well defined intermediate phenotypes in between. ColVI-myopathies also share common features with other disorders with prominent muscle contractures making differential diagnosis difficult. This group of disorders, under-recognized for a long time, has aroused much focus over the last decade with the important advances made in understanding its molecular pathogenesis. Indeed, numerous mutations have now been reported in the COL6A1, COL6A2 and COL6A3 genes, a large proportion of which are de novo and exert dominant negative effects. Genotype-phenotype correlations have also started to emerge and reflect the various pathogenic mechanisms at play in these disorders: dominant de novo exon splicing that enable the synthesis and secretion of mutant tetramers, as well as homozygous nonsense mutations leading to premature termination of translation and complete loss of function are associated with early onset, severe phenotypes. In this review, we will present the current state of diagnosis and research in the field of ColVI-myopathies. The past decade has provided significant advances with the identification of altered cellular functions in animal models of ColVI-myopathies and in patients' samples. In particular, mitochondrial dysfunction and a defect in the autophagic clearance system of skeletal muscle have recently been reported, thereby opening potential therapeutic avenues.
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Article dans une revue
Skeletal Muscle, BioMed Central, 2011, 1 (1), pp.30. 〈10.1186/2044-5040-1-30〉
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CEA | UPMC | U974

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Valérie Allamand, Laura Briñas, Pascale Richard, Tanya Stojkovic, Susana Quijano-Roy, et al.. ColVI-myopathies: where do we stand, where do we go?. Skeletal Muscle, BioMed Central, 2011, 1 (1), pp.30. 〈10.1186/2044-5040-1-30〉. 〈inserm-00630240〉

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