Bethlem myopathy

A hereditary myopathy characterized by skeletal muscle weakness and contractures of the finger, wrist, and ankle joints. Onset can be at any age; affected children may be delayed in reaching developmental milestones and most patients over age 50 have difficulty walking without assistance. Skin abnormalities such as follicular hyperkeratosis may occur in some cases. Mutations in the COL6A1, COL6A2, and COL6A3 genes have been identified. OMIM: 158810

Also Known As:

Networked: 127 relevant articles (0 outcomes, 5 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Scleroatonic muscular dystrophy
2.	Muscular Diseases (Myopathy)
3.	Limb-Girdle Muscular Dystrophies (Limb-Girdle Muscular Dystrophy)
4.	Contracture
5.	Muscular Dystrophies (Muscular Dystrophy)

Experts

1.	Bonaldo, Paolo: 17 articles (12/2021 - 12/2003)
2.	Merlini, Luciano: 13 articles (11/2020 - 12/2003)
3.	Bönnemann, Carsten G: 12 articles (01/2021 - 06/2002)
4.	Sabatelli, Patrizia: 12 articles (11/2020 - 11/2002)
5.	Bernardi, Paolo: 11 articles (12/2021 - 12/2003)
6.	Lamandé, Shireen R: 9 articles (01/2021 - 01/2002)
7.	Braghetta, Paola: 8 articles (12/2021 - 12/2003)
8.	Allamand, Valérie: 7 articles (01/2021 - 10/2010)
9.	Hu, Ying: 7 articles (01/2021 - 12/2009)
10.	Gualandi, Francesca: 7 articles (01/2019 - 02/2010)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Bethlem myopathy:

1.	CollagenIBA 01/01/2023 - "Bethlem myopathy (BM) is a disease that is caused by mutations in the collagen VI genes. " 01/01/2021 - "Bethlem myopathy (BM) is an autosomal dominant or autosomal recessive disorder and is usually associated with mutations in the collagen VI genes. " 01/01/2021 - "Three sibs presented with intermediate phenotype of collagen VI-related dystrophies (48, 53 and 2.5 years old) while the fourth sibling (58 years old) was classified as Bethlem myopathy with spine rigidity. " 09/01/2020 - "Coexistence of digenic mutations in the collagen VI genes (COL6A1 and COL6A3) leads to Bethlem myopathy." 01/01/2018 - "Mutation in the collagen XII gene (COL12A1) was recently reported to induce Bethlem myopathy. "
2.	Proteins (Proteins, Gene)FDA Link 03/03/2023 - "Our results demonstrate transcriptome profiling of Bethlem myopathy, and provide new insights into the path mechanism of Bethlem myopathy associated with non-protein coding RNAs." 04/01/2000 - "This suggests protein misfolding as a molecular basis for this particular mutation in Bethlem myopathy, in agreement with radioimmunoassay data showing reduced levels of domain N2 in cultured fibroblasts from two patients." 07/01/1999 - "The objective of this study was to determine whether an altered molecular structure of collagen type VI, characteristic of Bethlem myopathy, could influence the expression of the protein complex linking the extracellular matrix with the subsarcolemmal cytoskeleton. " 07/30/1999 - "These results provide the first evidence of the biosynthetic consequences of structural collagen VI mutations and suggest that functional protein haploinsufficiency may be a common pathogenic mechanism in Bethlem myopathy." 07/30/1999 - "Bethlem myopathy and engineered collagen VI triple helical deletions prevent intracellular multimer assembly and protein secretion."
3.	Collagen Type VIIBA 06/14/2005 - "The clustering of the mutations in a relatively narrow area of the three collagen type VI chains in patients with Bethlem myopathy (BM) suggests that mutations in different regions could result in different phenotypes or in no phenotype at all. " 04/01/2000 - "A single G1679E mutation in the amino-terminal globular domain N2 of the alpha3 chain of type VI collagen was found in a large family affected with Bethlem myopathy. " 05/01/1998 - "Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy." 09/01/1996 - "Previously, we have established genetic linkage between the genes encoding the three constituent alpha-chains of type VI collagen and Bethlem myopathy. " 04/01/2019 - "Bethlem myopathy represents the milder phenotype of collagen type VI-related myopathies. "
4.	Laminin (Merosin)IBA 07/01/1999 - "This study shows that Bethlem myopathy linked to chromosome 21 is associated with a secondary decrease in laminin beta 1 expression." 07/01/1999 - "Decreased expression of laminin beta 1 in chromosome 21-linked Bethlem myopathy." 09/01/1996 - "Analogous to the putative perturbation of the anchoring function of the dystrophin-associated complex in congenital muscular dystrophy with mutations in the alpha 2-subunit of laminin, our observations suggest a similar mechanism in Bethlem myopathy." 07/01/1999 - "Muscle biopsies of four patients affected by chromosome 21-linked Bethlem myopathy were investigated by means of immunohistochemistry, with monoclonal antibodies for laminin chains, dystrophin and dystrophin associated glycoproteins. " 03/01/2009 - "We initially present the main clinical and diagnostic data concerning the CMDs related to changes in the complex dystrophin-associated glycoproteins-extracellular matrix: CMD with merosin deficiency (CMD1A), collagen VI related CMDs (Ullrich CMD and Bethlem myopathy), CMDs with abnormal glycosylation of alpha-dystroglycan (Fukuyama CMD, Muscle-eye-brain disease, Walker-Warburg syndrome, CMD1C, CMD1D), and the much rarer CMD with integrin deficiency. "
5.	RNA (Ribonucleic Acid)IBA 03/03/2023 - "Six skeletal muscle samples from 3 patients with Bethlem myopathy and 3 control subjects were analyzed by RNA-sequencing. " 07/01/2011 - "RNA and protein studies were performed in blood macrophages from 5 patients previously diagnosed with either Ullrich congenital muscular dystrophy (UCMD) or Bethlem myopathy (BM). "
6.	Glycine (Aminoacetic Acid)FDA LinkGeneric 01/18/2002 - "In this study, we examined the consequences of Bethlem myopathy triple helical glycine mutations in the alpha1(VI) and alpha2(VI) chains, as well as engineered alpha3(VI) triple helical glycine mutations. " 01/18/2002 - "Kinked collagen VI tetramers and reduced microfibril formation as a result of Bethlem myopathy and introduced triple helical glycine mutations." 11/01/2013 - "Glycine substitutions in the conserved Gly-X-Y motif in the triple helical (TH) domain of collagen VI are the most commonly identified mutations in the collagen VI myopathies including Ullrich congenital muscular dystrophy, Bethlem myopathy, and intermediate (INT) phenotypes. " 01/18/2002 - "These results provide the first evidence of the biosynthetic consequences of collagen VI triple helical glycine mutations and indicate that Bethlem myopathy results not only from the synthesis of reduced amounts of structurally normal protein but also from the presence of mutant collagen VI in the extracellular matrix."
7.	Extracellular Matrix ProteinsIBA 02/13/2015 - "Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD) sit at opposite ends of a clinical spectrum caused by mutations in the extracellular matrix protein collagen VI. Bethlem myopathy is relatively mild, and patients remain ambulant in adulthood while many UCMD patients lose ambulation by their teenage years and require respiratory interventions. " 05/01/2013 - "Ullrich Congenital Muscular Dystrophy (UCMD), Bethlem Myopathy (BM), and Congenital Myosclerosis are diseases caused by mutations in the genes encoding the extracellular matrix protein collagen VI. A dystrophic mouse model, where collagen VI synthesis was prevented by targeted inactivation of the Col6a1 gene, allowed the investigation of pathogenesis, which revealed the existence of a Ca(2+)-mediated dysfunction of mitochondria and sarcoplasmic reticulum, and of defective autophagy. " 10/01/2010 - "Mutations in the genes encoding the extracellular matrix protein collagen VI (ColVI) cause a spectrum of disorders with variable inheritance including Ullrich congenital muscular dystrophy, Bethlem myopathy, and intermediate phenotypes. " 12/01/2008 - "Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM) are muscle diseases due to mutations in the genes encoding the extracellular matrix protein collagen VI. Generation of a dystrophic mouse model where collagen VI synthesis was prevented by genetic ablation of the Col6a1 gene allowed an investigation of pathogenesis, which revealed the existence of a Ca(2+)-mediated dysfunction of mitochondria and the sarcoplasmic reticulum. " 04/01/2008 - "Ullrich congenital muscular dystrophy and Bethlem myopathy are skeletal muscle diseases that are due to mutations in the genes encoding collagen VI, an extracellular matrix protein forming a microfibrillar network that is particularly prominent in the endomysium of skeletal muscle. "
8.	DystrophinIBA 09/01/1996 - "Analogous to the putative perturbation of the anchoring function of the dystrophin-associated complex in congenital muscular dystrophy with mutations in the alpha 2-subunit of laminin, our observations suggest a similar mechanism in Bethlem myopathy." 07/01/1999 - "Muscle biopsies of four patients affected by chromosome 21-linked Bethlem myopathy were investigated by means of immunohistochemistry, with monoclonal antibodies for laminin chains, dystrophin and dystrophin associated glycoproteins. " 03/01/2009 - "We initially present the main clinical and diagnostic data concerning the CMDs related to changes in the complex dystrophin-associated glycoproteins-extracellular matrix: CMD with merosin deficiency (CMD1A), collagen VI related CMDs (Ullrich CMD and Bethlem myopathy), CMDs with abnormal glycosylation of alpha-dystroglycan (Fukuyama CMD, Muscle-eye-brain disease, Walker-Warburg syndrome, CMD1C, CMD1D), and the much rarer CMD with integrin deficiency. "
9.	Glycoproteins (Glycoprotein)IBA 06/01/1999 - "Bethlem myopathy is caused by mutations in one of the three chains of collagen type VI. Here we report the clinical description and the molecular characterization of the defect in a two-generation Italian family in which a Gly-->Arg substitution disrupts the triple helix structure of the alpha 3 chain of collagen type VI, an ubiquitous glycoprotein of the extracellular matrix. " 07/01/1999 - "Muscle biopsies of four patients affected by chromosome 21-linked Bethlem myopathy were investigated by means of immunohistochemistry, with monoclonal antibodies for laminin chains, dystrophin and dystrophin associated glycoproteins. " 03/01/2009 - "We initially present the main clinical and diagnostic data concerning the CMDs related to changes in the complex dystrophin-associated glycoproteins-extracellular matrix: CMD with merosin deficiency (CMD1A), collagen VI related CMDs (Ullrich CMD and Bethlem myopathy), CMDs with abnormal glycosylation of alpha-dystroglycan (Fukuyama CMD, Muscle-eye-brain disease, Walker-Warburg syndrome, CMD1C, CMD1D), and the much rarer CMD with integrin deficiency. "
10.	Dystroglycans (Dystroglycan)IBA 03/01/2009 - "We initially present the main clinical and diagnostic data concerning the CMDs related to changes in the complex dystrophin-associated glycoproteins-extracellular matrix: CMD with merosin deficiency (CMD1A), collagen VI related CMDs (Ullrich CMD and Bethlem myopathy), CMDs with abnormal glycosylation of alpha-dystroglycan (Fukuyama CMD, Muscle-eye-brain disease, Walker-Warburg syndrome, CMD1C, CMD1D), and the much rarer CMD with integrin deficiency. " 06/01/2002 - "This update focuses on the dystrophin-associated proteins including the dystroglycan and sarcoglycan complexes, caveolin-3, dysferlin, and the extracellular matrix component collagen type VI. The molecular findings are correlated with some of the clinical phenotypes that are part of the limb-girdle muscular dystrophy spectrum, including fukutin-related proteinopathy (LGMD 21), the sarcoglycanopathies (LGMD 2C-F), caveolinopathy (LGMD 1C), dysferlinopathy (LGMD 2B), and finally Bethlem myopathy. "

Therapies and Procedures

1.

Therapeutics 07/01/2009 - "They represent an essential step towards an effective therapy for Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy, because Debio 025 does not expose patients to the potentially harmful effects of immunosuppression." 10/15/2014 - "Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are inherited muscle diseases due to mutations in the genes encoding the extracellular matrix protein collagen (Col) VI. Opening of the cyclosporin A-sensitive mitochondrial permeability transition pore (PTP) is a causative event in disease pathogenesis, and a potential target for therapy. "