Ullrich congenital muscular dystrophy

Endoplasmic reticulum stress is an emerging significant player in the molecular pathology of connective tissue disorders. In response to endoplasmic reticulum stress, cells can upregulate macroautophagy/autophagy, a fundamental cellular homeostatic process used by cells to degrade and recycle proteins or remove damaged organelles. In these scenarios, autophagy activation can support cell survival. Here we demonstrated by in vitro and in vivo approaches that megakaryocytes derived from col6a1 -⁄- (collagen, type VI, alpha 1) null mice display increased intracellular retention of COL6 polypeptides, endoplasmic reticulum stress and apoptosis...

Mutations in the genes encoding collagen VI cause Bethlem myopathy (MIM 158810), Ullrich congenital muscular dystrophy (MIM 254090), and myosclerosis myopathy (MIM #255600). BM is a dominantly inherited disorder, characterised by proximal muscle weakness and joint contractures mainly involving the elbows, ankles, and fingers, which usually follows a relatively mild course. By contrast, UCMD is a severe muscular dystrophy characterized by early onset, rapidly progressive muscle wasting and weakness, proximal joint contractures and distal joint hyperlaxity...

We present the case of a 19-year-old female with Ullrich congenital muscular dystrophy (UCMD1, a collagen VI defect) who developed a right-sided pneumothorax after choking on a piece of meat. She received two chest tubes (pigtails) that resolved the pneumothorax. She was discharged in stable condition, and a chest radiograph two weeks later showed total resolution of the pneumothorax. Two months after this episode, the patient presented with another small, right-sided pneumothorax that shortly progressed to extension throughout the right side of the chest...

Collagen VI-related dystrophies (COL6-RDs) are a group of rare congenital neuromuscular dystrophies that represent a continuum of overlapping clinical phenotypes that go from the milder Bethlem myopathy (BM) to the severe Ullrich congenital muscular dystrophy, for which there is no effective treatment. Mutations in one of the three Collagen VI genes alter the incorporation of this protein into the extracellular matrix (ECM), affecting the assembly and the structural integrity of the whole fibrillar network...

BACKGROUND: Ullrich congenital muscular dystrophy (UCMD) is one of the collagen-VI-related myopathies caused by mutations of COL6A1 , COL6A2 , and COL6A3 genes. Affected individuals are characterized by muscle weakness, proximal joint contracture, distal joint hyperlaxity, and progressive respiratory failure. There is currently no cure for UCMD. Here, we report the clinical manifestations and prenatal diagnosis of compound heterozygous mutations of the COL6A2 gene in a Chinese family with UCMD...

We report a newborn born to a consanguineous couple with antenatally detected dilatation of third ventricle, unilateral talipes, and intra uterine growth retardation. On examination, there was facial dysmorphism, hypotonia, encephalopathy, joint laxity and muscle hypertrophy in addition to left foot talipes. On evaluation, there were renal cortical cysts, rhizomelia, chondrodysplasia punctata and elevated muscle enzymes, along with a dilated third ventricle. As the phenotype was not consistent with any of the muscular dystrophies or the peroxisomal disorders, an exome sequencing was requested...

Keratosis pilaris is a common skin condition associated with a number of syndromes, including collagen type VI-related disorders. Our patient, recently diagnosed with Ullrich congenital muscular dystrophy, presented with severe keratosis pilaris, hypotonia, and velvety skin on the palms and soles. We present this case to highlight the importance of including cutaneous findings, such as keratosis pilaris, to aid in the diagnosis when evaluating patients with syndromic features.

Collagen VI is distributed in the interstitium and is secreted mainly by mesenchymal stromal cells (MSCs) in skeletal muscle. Mutations in COL6A1-3 genes cause a spectrum of COL6-related myopathies. In this study, we performed a systemic transplantation study of human-induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) into neonatal immunodeficient COL6-related myopathy model ( Col6a1 KO /NSG) mice to validate the therapeutic potential. Engraftment of the donor cells and the resulting rescued collagen VI were observed at the quadriceps and diaphragm after intraperitoneal iMSC transplantation...

Mutations in the genes encoding the major collagen VI isoform, COL6A1, COL6A2 and COL6A3, are responsible for the muscle disorders Bethlem myopathy and Ullrich congenital muscular dystrophy. These disorders form a disease spectrum from mild to severe. Dominant and recessive mutations are found along the entire spectrum and the clinical phenotype is strongly influenced by the way mutations impede collagen VI protein assembly. Most mutations are in the triple helical domain, towards the N-terminus and they compromise microfibril assembly...

OBJECTIVES: Collagen-VI-related myopathies are caused by both dominant and recessive mutations in the three collagen-VI-related genes (COL6A1, COL6A2, and COL6A3) and present as two different major clinical entities; Bethlem myopathy and Ullrich congenital muscular dystrophy. METHODS: In this study, we evaluated the clinical, pathologic, and genetic features of 8 patients with Bethlem myopathy from 3 families. RESULTS: We inspected disease course differences with age and mutations...

Hemostatic abnormalities and impaired platelet function have been described in patients affected by connective tissue disorders. We observed a moderate bleeding tendency in patients affected by collagen VI-related disorders and investigated the defects in platelet functionality, whose mechanisms are unknown. We demonstrated that megakaryocytes express collagen VI that is involved in the regulation of functional platelet production. By exploiting a collagen VI-null mouse model (Col6a1-/-), we found that collagen VI-null platelets display significantly increased susceptibility to activation and intracellular calcium signaling...

BACKGROUND: Mesenchymal stromal cells (MSCs) function as supportive cells on skeletal muscle homeostasis through several secretory factors including type 6 collagen (COL6). Several mutations of COL6A1, 2, and 3 genes cause Ullrich congenital muscular dystrophy (UCMD). Skeletal muscle regeneration deficiency has been reported as a characteristic phenotype in muscle biopsy samples of human UCMD patients and UCMD model mice. However, little is known about the COL6-dependent mechanism for the occurrence and progression of the deficiency...

Patients with preexisting respiratory compromise are at risk for perioperative respiratory failure. Adult literature has shown benefit with prophylactic postoperative use of noninvasive mechanical ventilation (NIMV). While pediatric literature has documented the increasing use of postoperative NIMV, there is no literature on prophylactic preoperative NIMV in patients with preexisting respiratory compromise. Further, surgical literature does not address preoperative prophylactic use of NIMV, as well as use of the newest modality of NIMV, average volume-assured pressure support (AVAPS)...

OBJECTIVE: Immunocharacterization of congenital muscular dystrophy (CMD) to determine the frequency of various subtypes in a large Indian Cohort. MATERIALS AND METHODS: This retrospective (2014-2017) study was carried on muscle biopsies of clinically suspected cases of CMD with histological evidence of dystrophy/myopathic features. Immunohistochemistry (IHC) to antibodies against laminin (α2, α5,β1,γ1), Collagen-VI (A1,2,3), and Western blot (WB) for α-dystroglycan and POMT1 was performed...

Type VI collagen (collagen VI) is an obligate extracellular matrix component found mainly in the basement membrane region of many mammalian tissues and organs, including skeletal muscle and throughout the respiratory system. Collagen VI is probably most recognized in medicine as the genetic cause of a spectrum of muscular dystrophies, including Ullrich Congenital Myopathy and Bethlem Myopathy. Collagen VI is thought to contribute to myopathy, at least in part, by mediating muscle fiber integrity by anchoring myoblasts to the muscle basement membrane...

BACKGROUND: Collagen VI-related dystrophy spans a clinical continuum from severe Ullrich congenital muscular dystrophy to milder Bethlem myopathy. This disease is caused by causative variants in COL6A1, COL6A2, or COL6A3. Most reported causative variants are de novo; therefore, to identify possible associated causative variants, comprehensive large cohort studies are required for different ethnicities. METHODS: We retrospectively reviewed clinical information, muscle histology, and genetic analyses from 147 Japanese patients representing 130 families, whose samples were sent for diagnosis to the National Center of Neurology and Psychiatry between July 1979 and January 2020...

Scoliosis in Ullrich Congenital Muscular Dystrophy (UCMD) is very common, with a reported incidence of more than 50%, and it is rapidly progressive. There are no previous studies which specifically focus on scoliosis surgery in UCMD patients. This article reports three cases of scoliosis surgery in UCMD, focusing on operative course, clinical and radiological results achieved, fusion area and complications, with a 2-year follow-up. The surgical technique adopted for vertebral arthrodesis included: high-density pedicle screw systems, asymmetric rods contouring and direct vertebral rotation...

BACKGROUND: Collagen VI-related dystrophies are a subtype of congenital muscular dystrophy caused by pathogenic variants in COL6A1, COL6A2 or COL6A3 genes affecting skeletal muscles and connective tissue. The clinical phenotype ranges from the milder Bethlem myopathy to the severe Ullrich congenital muscular dystrophy (UCMD). Herein, we report the first consanguineous Sri Lankan family with two children affected with UCMD due to a novel variant in the COL6A1 gene. CASE PRESENTATION: Two sisters, aged 10-years and 7-years, presented with progressive, bilateral proximal muscle weakness...

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OBJECTIVE: To accurately categorize the phenotypes of individuals with collagen VI-related dystrophies (COL6-RDs) during the first years of life in order to predict long-term motor function and pulmonary function, provide phenotype-specific anticipatory care and improve clinical trial readiness. METHODS: This retrospective, multicenter, international study analyzed the relationship of long-term motor and pulmonary function with the initial maximal motor ability achieved in individuals with COL6-RD...