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

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 myopathi...

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Main Authors:	Allamand, Valérie, Briñas, Laura, Richard, Pascale, Stojkovic, Tanya, Quijano-Roy, Susana, Bonne, Gisèle
Format:	Online
Language:	English
Published:	BioMed Central 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189202/

id	pubmed-3189202
recordtype	oai_dc
spelling	pubmed-31892022011-10-08 ColVI myopathies: where do we stand, where do we go? Allamand, Valérie Briñas, Laura Richard, Pascale Stojkovic, Tanya Quijano-Roy, Susana Bonne, Gisèle Review 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 associated with prominent muscle contractures, making differential diagnosis difficult. This group of disorders, under-recognized for a long time, has aroused much interest over the past decade, with 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, which reflect the various pathogenic mechanisms at play in these disorders: dominant de novo exon splicing that enables the synthesis and secretion of mutant tetramers and homozygous nonsense mutations that lead to premature termination of translation and complete loss of function are associated with early-onset, severe phenotypes. In this review, we 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 patient 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. BioMed Central 2011-09-23 /pmc/articles/PMC3189202/ /pubmed/21943391 http://dx.doi.org/10.1186/2044-5040-1-30 Text en Copyright ©2011 Allamand et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Allamand, Valérie Briñas, Laura Richard, Pascale Stojkovic, Tanya Quijano-Roy, Susana Bonne, Gisèle
spellingShingle	Allamand, Valérie Briñas, Laura Richard, Pascale Stojkovic, Tanya Quijano-Roy, Susana Bonne, Gisèle ColVI myopathies: where do we stand, where do we go?
author_facet	Allamand, Valérie Briñas, Laura Richard, Pascale Stojkovic, Tanya Quijano-Roy, Susana Bonne, Gisèle
author_sort	Allamand, Valérie
title	ColVI myopathies: where do we stand, where do we go?
title_short	ColVI myopathies: where do we stand, where do we go?
title_full	ColVI myopathies: where do we stand, where do we go?
title_fullStr	ColVI myopathies: where do we stand, where do we go?
title_full_unstemmed	ColVI myopathies: where do we stand, where do we go?
title_sort	colvi myopathies: where do we stand, where do we go?
description	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 associated with prominent muscle contractures, making differential diagnosis difficult. This group of disorders, under-recognized for a long time, has aroused much interest over the past decade, with 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, which reflect the various pathogenic mechanisms at play in these disorders: dominant de novo exon splicing that enables the synthesis and secretion of mutant tetramers and homozygous nonsense mutations that lead to premature termination of translation and complete loss of function are associated with early-onset, severe phenotypes. In this review, we 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 patient 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.
publisher	BioMed Central
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189202/
_version_	1611479617721335808

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

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