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Diaphragm Ultrasound in Patients with Neuromuscular Disorders
Published in Massimo Zambon, Ultrasound of the Diaphragm and the Respiratory Muscles, 2022
Collagen VI myopathy is another hereditary myopathy that can affect diaphragm function (28). Collagen VI myopathy is in relation to mutations in the COL6A1-3 genes. These diseases include Ullrich congenital muscular dystrophy, the most severe form, and Bethlem myopathy, the milder form (28).
Muscular Dystrophy Diseases
Published in Maher Kurdi, Neuromuscular Pathology Made Easy, 2021
The most common types of CMD are group 1 (Table 16.1). Because their antibodies are commercially available, the diagnosis can be made through IHC. In collage VI deficiency (Ulrich syndrome), the collagen immunolabeling pattern is always weak. Because Ulrich syndrome and Bethlem myopathy are closely related in clinical ground, the effect of a particular mutation on the production and function of collagen VI may determine the severity. In general, the immunolabeling pattern of collagen VI is always unequivocal or may show some reduction. Nevertheless, collagen VI could be normal in Bethlem myopathy. To help differentiate Ulrich from Bethlem myopathies, Lamin B1 is used commonly as a secondary labeling index in Bethlem myopathy, which shows a reduction in staining pattern.
Neurology
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Fenella Kirkham, Adnan Manzur, Stephanie Robb
Limb girdle dystrophies (LGMD) (Figs 8.55, 8.60): dominant and recessive forms, many subtypes, some present in adulthood.abnormalities of: – lamin A/C (Emery–Dreifuss dystrophy (EDMD)) (Figs 8.60 C,D 8.26 C,D).– calpain 3 (Figs 8.60 E,F).– sarcoglycans (Figs 8.60 A,B,G,D).– FKRP.– collagen VI (Bethlem myopathy).
Translational readthrough inducing drugs for the treatment of inherited retinal dystrophies
Published in Expert Review of Ophthalmology, 2020
Christopher M Way, Dulce Lima Cunha, Mariya Moosajee
PTC-containing transcripts are typically degraded by NMD, reducing their availability. Therefore, inhibition of NMD is proposed to increase mRNA stability and as a consequence, increase the amount of substrate for TRIDs to target. Caffeine inhibits NMD through the inhibition of SMG1 kinase [35,36] (Figure 2(c)). It alone has been shown to rescue the phenotype in fibroblasts carrying a PTC seen in the muscular dystrophy Ullrich’s disease, by increasing mRNA and protein levels of the defective collagen VI α2 [37]. NMDI1 is a tetracyclic compound that traps UPF1 in a hyperphosphorylated state, preventing downstream interactions with SMG5 [38] (Figure 2(d)). It is specific for NMD, does not affect translation efficiency and is non-cytotoxic [38]. In a mouse model of Mucopolysacchardisosis I-Hurler syndrome (MPS I-H) that carries the knock-in Idua p.W392* mutation, NMDI1 application with gentamicin resulted in greater readthrough and functional enzymatic activity than gentamicin alone [39]. However, NMDI1 synthesis is inefficient and technically difficult. In contrast, VG1, a structural analogue of NMDI1 with similar inhibition capability, is more easily produced and shows an improved yield [40]. Its mechanism of action is currently unknown but its application to IRDs is awaited. Amlexanox is a compound with both readthrough and NMD inhibition properties. It has been reported as a combined therapy option for PTCs causing cystic fibrosis (CF) and recessive dystrophic epidermolysis bullosa, showing increased levels of full-length proteins compared to G418 and PTC124 alone [41,42].
Extracellular Matrix Remodeling During Palate Development
Published in Organogenesis, 2020
Xia Wang, Chunman Li, Zeyao Zhu, Li Yuan, Wood Yee Chan, Ou Sha
Collagens are the major components of ECM in connective tissues. There are 28 distinct collagens composed of α1, α2, α3 subunits combination and classified into fibrillar collagens (Collagen I–III, V, and XI) and non-fibrillar forms (Collagen VI, IX, IV, etc.).5,19 Fibrillar collagens form strong and stable fibrils and organize the fibrils into three-dimensional network, for example, Collagen I fibrils for bones and Collagen II fibrils for cartilages.5 Non-fibrillar forms of collagens include Fibril-Associated Collagens and basement collagens. Fibril-Associated Collagens, such as Collagen IX, associate with collagen fibrils and bind them together to form thicker collagen fibers. Basement collagens are sheet-forming collagens such as Collagen IV, which form the two-dimensional network for all basal laminae.5,19 A variety of collagens are highly expressed in the palate and dynamically remodeled during palatogenesis (Tables 1 and 2).
The clinical and molecular spectrum of autosomal dominant limb-girdle muscular dystrophies focusing on transportinopathy
Published in Expert Opinion on Orphan Drugs, 2019
Corrado Angelini, Valentina Pegoraro, Giovanna Cenacchi
In the diagnostic approach the patients with dominant limb-girdle weakness one have to consider: Bethlem myopathy [51] that has a variable degree of muscle weakness affecting legs and arms. The patients develop contractures of hand joints and there is the tightness of Achilles tendon. This dominant form due to a mutation of Collagen VI has also been renamed LGMD D5 in the new ENMC classification.Emery-Dreifuss dystrophy [52] has an early humeroperoneal weakness, limb contractures due to lamin A/C mutation that might share overlapping clinical features with dominant LGMD. It has both an X-linked or autosomal dominant inheritance, but usually presents a prominent heart involvement with conduction block, episodes of fainting, neck and elbow contractures.Facioscapulohumeral Dystrophy [53] is most frequently inheritable muscular dystrophy and typically affects facial scapulohumeral, tibial muscles. It might be confused with an LGMD since in severe cases both shoulder and pelvic girdles are involved. However, facial weakness is absent in LGMD, while asymmetric facial and limb involvement is almost invariably present in FSHD cases.