Scleroatonic muscular dystrophy

A genetically heterogeneous hereditary form of muscular dystrophy that is characterized by multiple CONTRACTURES; HYPOTONIA; HIP DISLOCATION and TORTICOLLIS beginning in infancy. RESPIRATORY INSUFFICIENCY and PNEUMONIA are also common. Mutations in the COL6A1, COL6A2, and COL6A3 genes have been identified. OMIM: 254090

Also Known As:

Networked: 137 relevant articles (0 outcomes, 7 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Muscular Dystrophies (Muscular Dystrophy)
2.	Bethlem myopathy
3.	Muscular Diseases (Myopathy)
4.	Mitochondrial Diseases (Mitochondrial Disease)
5.	Duchenne Muscular Dystrophy (Muscular Dystrophy, Becker)

Experts

1.	Bonaldo, Paolo: 22 articles (12/2021 - 12/2003)
2.	Sabatelli, Patrizia: 21 articles (01/2022 - 11/2002)
3.	Merlini, Luciano: 19 articles (01/2022 - 12/2003)
4.	Bernardi, Paolo: 14 articles (12/2021 - 12/2003)
5.	Bönnemann, Carsten G: 13 articles (01/2021 - 08/2003)
6.	Muntoni, Francesco: 13 articles (01/2020 - 06/2004)
7.	Gualandi, Francesca: 11 articles (01/2019 - 01/2007)
8.	Hu, Ying: 9 articles (01/2021 - 09/2008)
9.	Ferlini, Alessandra: 9 articles (01/2019 - 01/2007)
10.	Bertini, Enrico: 9 articles (04/2016 - 01/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Scleroatonic muscular dystrophy:

1.	Cyclosporine (Ciclosporin)FDA LinkGeneric 01/01/2011 - "Cyclosporine A in Ullrich congenital muscular dystrophy: long-term results." 01/16/2007 - "This study represents an essential step toward a pharmacological therapy of Ullrich congenital muscular dystrophy with cyclosporin A and methylAla(3)ethylVal(4) cyclosporin." 01/01/2009 - "Cyclosporine A treatment for Ullrich congenital muscular dystrophy: a cellular study of mitochondrial dysfunction and its rescue." 01/01/2011 - "Six individuals with Ullrich congenital muscular dystrophy (UCMD) and mutations in the genes-encoding collagen VI, aging 5-9, received 3-5 mg/kg of cyclosporine A (CsA) daily for 1 to 3.2 years. " 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. "
2.	Small Interfering RNA (siRNA)IBA 11/01/2006 - "In this study, we evaluated the effect of NMD inhibition on the phenotype of Ullrich disease, an autosomal recessive congenital muscular dystrophy, by pharmacological inhibition of SMG-1 or siRNA-mediated knockdown of SMG-1 or Upf1. " 09/01/2006 - "In this study, we evaluated the effects of NMD inhibition by siRNA-mediated knockdown of SMG-1 or Upf1 on the phenotype of Ullrich disease, an autosomal recessive congenital muscular dystrophy. " 01/01/2023 - ": 7-AAD: 7-amino-actinomycin D; ATF: activating transcriptional factor; BAX: BCL2 associated X protein; BCL2: B cell leukemia/lymphoma 2; BCL2L1/Bcl-xL: BCL2-like 1; BM: bone marrow; COL6: collagen, type VI; col6a1-⁄-: mice that are null for Col6a1; DDIT3/CHOP/GADD153: DNA-damage inducible transcript 3; EGFP: enhanced green fluorescent protein; ER: endoplasmic reticulum; reticulophagy: endoplasmic reticulum-selective autophagy; HSPA5/Bip: heat shock protein 5; HSP90B1/GRP94: heat shock protein 90, beta (Grp94), member 1; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; Mk: megakaryocytes; MTOR: mechanistic target of rapamycin kinase; NIMV: noninvasive mechanical ventilation; PI3K: phosphoinositide 3-kinase; PPP1R15A/GADD34: protein phosphatase 1, regulatory subunit 15A; RT-qPCR: reverse transcription-quantitative real-time PCR; ROS: reactive oxygen species; SERPINH1/HSP47: serine (or cysteine) peptidase inhibitor, clade H, member 1; sh-RNA: short hairpin RNA; SOCE: store operated calcium entry; UCMD: Ullrich congenital muscular dystrophy; UPR: unfolded protein response; WIPI2: WD repeat domain, phosphoinositide-interacting 2; WT: wild type; XBP1: X-box binding protein 1."
3.	CollagenIBA 09/21/2023 - "Ullrich congenital muscular dystrophy (UCMD) is a rare type of autosomal dominant or recessive CMDs, mainly caused by mutations in the related genes leading to loss of collagen VI with an earlier onset time and progressive clinical symptoms(1, 3). " 01/01/2021 - "All affected dogs were homozygous for the p.Glu97* nonsense variant in the COL6A1 gene encoding the alpha-1 chain of collagen VI. Muscle biopsies revealed alterations similar to those in human patients with Ullrich congenital muscular dystrophy including the virtual absence of collagen VI in skeletal muscles. " 01/01/2016 - "Similar results were obtained after in vitro perturbation of collagen VI extracellular assembly with the 3C4 anti-collagen VI antibody and in collagen VI-deficient tendon cultures of a Ullrich congenital muscular dystrophy patient carrying mutations in COL6A2 gene. " 03/01/2015 - "Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in either COL6A1, COL6A2 or COL6A3 gene, thereby leading to collagen VI deficiency in the ECM. " 05/01/2014 - "Novel collagen VI mutations identified in Chinese patients with Ullrich congenital muscular dystrophy."
4.	Proteins (Proteins, Gene)FDA Link 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). " 01/01/2018 - "In vivo, ColVI deficiency causes fragmentation of acetylcholine receptor (AChR) clusters, with abnormal expression of NMJ-enriched proteins and re-expression of fetal AChRγ subunit, both in Col6a1 null mice and in patients affected by Ullrich congenital muscular dystrophy (UCMD), the most severe form of ColVI-related myopathies. " 11/01/2010 - "Furthermore, muscle biopsies from subjects with Bethlem myopathy or Ullrich congenital muscular dystrophy had reduced protein amounts of beclin-1 and Bnip3. " 01/01/2006 - "We also demonstrated that transfection of the suppressor tRNA to Ullrich disease fibroblasts, possessing a frameshift mutation in the collagen VI alpha2 gene, induced the upregulation of the collagen VI alpha2 mRNA and accumulation of the collagen VI protein. "
5.	RNA (Ribonucleic Acid)IBA 09/21/2023 - "Unexpected partial RNA deletion by two different novel COL6A2 mutations leads to Ullrich congenital muscular dystrophy." 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). " 01/01/2023 - ": 7-AAD: 7-amino-actinomycin D; ATF: activating transcriptional factor; BAX: BCL2 associated X protein; BCL2: B cell leukemia/lymphoma 2; BCL2L1/Bcl-xL: BCL2-like 1; BM: bone marrow; COL6: collagen, type VI; col6a1-⁄-: mice that are null for Col6a1; DDIT3/CHOP/GADD153: DNA-damage inducible transcript 3; EGFP: enhanced green fluorescent protein; ER: endoplasmic reticulum; reticulophagy: endoplasmic reticulum-selective autophagy; HSPA5/Bip: heat shock protein 5; HSP90B1/GRP94: heat shock protein 90, beta (Grp94), member 1; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; Mk: megakaryocytes; MTOR: mechanistic target of rapamycin kinase; NIMV: noninvasive mechanical ventilation; PI3K: phosphoinositide 3-kinase; PPP1R15A/GADD34: protein phosphatase 1, regulatory subunit 15A; RT-qPCR: reverse transcription-quantitative real-time PCR; ROS: reactive oxygen species; SERPINH1/HSP47: serine (or cysteine) peptidase inhibitor, clade H, member 1; sh-RNA: short hairpin RNA; SOCE: store operated calcium entry; UCMD: Ullrich congenital muscular dystrophy; UPR: unfolded protein response; WIPI2: WD repeat domain, phosphoinositide-interacting 2; WT: wild type; XBP1: X-box binding protein 1."
6.	MicroRNAs (MicroRNA)IBA 10/01/2020 - "This study aimed to identify the common miRNA signatures that are associated with mitochondrial damage in different muscular dystrophies (MDs; Duchenne muscular dystrophy, megaconial congenital muscular dystrophy, Ullrich congenital muscular dystrophy, and α-dystroglycanopathy). "
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.	Collagen Type VIIBA 09/15/2017 - "Dominant-negative mutations in the genes that encode the three major α chains of collagen type VI, COL6A1, COL6A2, and COL6A3, account for more than 50% of Ullrich congenital muscular dystrophy patients and nearly all Bethlem myopathy patients. " 09/10/2013 - "We evaluated the knockdown of 15 NMD components in Ullrich congenital muscular dystrophy fibroblasts, which have a homozygous frameshift mutation causing a PTC in the collagen type VI α 2 gene. " 11/15/2002 - "We recently reported a severe deficiency in collagen type VI, resulting from recessive mutations of the COL6A2 gene, in patients with Ullrich congenital muscular dystrophy. " 06/19/2001 - "Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI." 01/01/2002 - "Collagen type VI and related disorders: Bethlem myopathy and Ullrich scleroatonic muscular dystrophy."
9.	Messenger RNA (mRNA)IBA 06/24/2014 - "Allele-specific Gene Silencing of Mutant mRNA Restores Cellular Function in Ullrich Congenital Muscular Dystrophy Fibroblasts." 04/11/2014 - "The resulting heterozygous mouse, Col6a3(+/d16), produced comparable amounts of normal Col6a3 mRNA and a mutant transcript with an in-frame deletion of 54 bp of triple-helical coding sequences, thus mimicking the most common molecular defect found in dominant Ullrich congenital muscular dystrophy patients. " 01/01/2006 - "We also demonstrated that transfection of the suppressor tRNA to Ullrich disease fibroblasts, possessing a frameshift mutation in the collagen VI alpha2 gene, induced the upregulation of the collagen VI alpha2 mRNA and accumulation of the collagen VI protein. "
10.	Glycine (Aminoacetic Acid)FDA LinkGeneric 09/01/2008 - "Glycine mutations in the triple helix have been identified in both Bethlem and Ullrich congenital muscular dystrophy, but it is not known why they cause these different phenotypes. " 09/01/2005 - "Here, for the first time, we report a genotype-phenotype correlation demonstrating that heterozygous glycine substitutions in the triple-helix domain of COL6A1 are dominant and responsible for a milder Ullrich scleroatonic muscular dystrophy phenotype, and that recessive mutations in COL6A1 correlate with more severe clinical and biochemical Ullrich scleroatonic muscular dystrophy phenotypes." 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. "

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." 01/16/2007 - "This study represents an essential step toward a pharmacological therapy of Ullrich congenital muscular dystrophy with cyclosporin A and methylAla(3)ethylVal(4) cyclosporin." 01/16/2007 - "Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins." 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. "
2.	Anesthesia 10/01/2022 - "[Anesthesia for thoracic surgery in a female patient with Ullrich congenital muscular dystrophy]." 01/01/2021 - "Anesthesia and Ullrich Congenital Muscular Dystrophy: Comment."
3.	Noninvasive Ventilation 12/01/2013 - "Nocturnal non-invasive ventilation was initiated in patients with Ullrich congenital muscular dystrophy by 11.3 years (±4.0) and in patients with intermediate collagen VI-related myopathy by 20.7 years (±1.5). "
4.	Perioperative Care 06/01/2009 - "Perioperative care of a child with Ullrich congenital muscular dystrophy."
5.	Cell Transplantation 01/01/2021 - "Collagen-VI supplementation by cell transplantation improves muscle regeneration in Ullrich congenital muscular dystrophy model mice."