The collagen VI-related myopathies

Bönnemann, Carsten G.

doi:10.1016/b978-0-08-045031-5.00005-0

Cited by 89 publications

(44 citation statements)

References 111 publications

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“…Given the early onset and progressive course of COL6-related myopathies, patients typically get worse with time, but not in a predictable way 1 . LPD treatment is expected to enhance autophagy-mediated protein and organelle breakdown and, as a consequence, patients lost 7% of muscle mass.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations of COL6 genes ( COL6A1, COL6A2 , and COL6A3 ) cause COL6-related myopathies, 1 a group of rare inherited muscle diseases that include Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), as well as the limb girdle and myosclerosis myopathy variants 2,3 . BM is characterized by axial and proximal muscle weakness, 4,5 together with contractures of the interphalangeal joints of the last 4 fingers 6 .…”

Section: Introductionmentioning

confidence: 99%

“…UCMD is a severe congenital muscular dystrophy characterized by early onset, generalized muscle wasting and weakness, proximal joint contractures and distal joint hyperflexibility. Independent walking is rarely achieved or maintained in UCMD children, who also suffer from early and progressive respiratory failure 1,8 . There is currently no cure for BM or UCMD 9 …”

Section: Introductionmentioning

confidence: 99%

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Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial

Castagnaro

Pellegrini

et al. 2016

Autophagy

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A pilot clinical trial based on nutritional modulation was designed to assess the efficacy of a one-year low-protein diet in activating autophagy in skeletal muscle of patients affected by COL6/collagen VI-related myopathies. Ullrich congenital muscular dystrophy and Bethlem myopathy are rare inherited muscle disorders caused by mutations of COL6 genes and for which no cure is yet available. Studies in col6 null mice revealed that myofiber degeneration involves autophagy defects and that forced activation of autophagy results in the amelioration of muscle pathology. Seven adult patients affected by COL6 myopathies underwent a controlled low-protein diet for 12 mo and we evaluated the presence of autophagosomes and the mRNA and protein levels for BECN1/Beclin 1 and MAP1LC3B/LC3B in muscle biopsies and blood leukocytes. Safety measures were assessed, including muscle strength, motor and respiratory function, and metabolic parameters. After one y of low-protein diet, autophagic markers were increased in skeletal muscle and blood leukocytes of patients. The treatment was safe as shown by preservation of lean:fat percentage of body composition, muscle strength and function. Moreover, the decreased incidence of myofiber apoptosis indicated benefits in muscle homeostasis, and the metabolic changes pointed at improved mitochondrial function. These data provide evidence that a low-protein diet is able to activate autophagy and is safe and tolerable in patients with COL6 myopathies, pointing at autophagy activation as a potential target for therapeutic applications. In addition, our findings indicate that blood leukocytes are a promising noninvasive tool for monitoring autophagy activation in patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial

Castagnaro

Pellegrini

et al. 2016

Autophagy

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“…2 9 Übersicht über die vielschichtigen Lagen der extrazellulären Matrix im Skelettmuskel und über die pathophysiologischen Sekundäreffekte von Dystrophinmangel auf das Skelettmuskelgewebe broblasten eine entscheidende Rolle bei neuromuskulären Erkrankungen [4].…”

Section: Der Pathologe 1 · 2017 21unclassified

“…Genetische Muskelerkrankungen mit primären Defekten in spezifischen Kollagenen sind die Bethlem-Myopathie und die kongenitale Muskeldystrophie Typ Ulrich mit einer spezifischen Defizienz im Kollagen VI [2]. Im Gegensatz zum genetisch verursachten Verlust von Kollagen bei der kongenitalen Muskeldystrophie [3] kann bei einer progredienten Muskelschädigung die pathobiochemische Akkumulation dieses extrazellulären Proteins eine reaktive Myofibrose verursachen [4].…”

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Molekulare Pathogenese der Fibrose bei Muskeldystrophie vom Typ Duchenne

Ohlendieck

Swandulla

2017

Pathologe

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Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy

Mohan,

McNulty,

Thaxton

et al. 2024

Ann Clin Transl Neurol

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ObjectiveLimb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD.MethodsThe ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene–disease relationships (GDR) using the ClinGen gene–disease clinical validity framework to evaluate 31 genes implicated in LGMD.ResultsThe GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes (CAPN3, COL6A1, COL6A2, and COL6A3) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as definitive, 4 (11%) as moderate, and 1 (3%) as limited. Two genes, POMGNT1 and DAG1, though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD.InterpretationThe expert‐reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case‐level data that help clarify disputed or novel LGMD associations.

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The collagen VI-related myopathies

Cited by 89 publications

References 111 publications

Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial

Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial

Molekulare Pathogenese der Fibrose bei Muskeldystrophie vom Typ Duchenne

Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy

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