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Genetics
Published in Ibrahim Natalwala, Ammar Natalwala, E Glucksman, MCQs in Neurology and Neurosurgery for Medical Students, 2022
Ibrahim Natalwala, Ammar Natalwala, E Glucksman
TRUE – Both Becker’s and Duchenne muscular dystrophy are X-linked recessive inherited diseases that have genetic mutations of the dystrophin (DMD) gene. In Duchenne muscular dystrophy, there is usually no production of functional dystrophin and hence there is a more severe loss of muscle fibres and greater severity of symptoms. Onset of Becker’s is in adolescence whereas in Duchenne onset is commonly in early childhood.5Remember: Duchenne – Deleted Muscle Dystrophin (DMD gene)
Anaesthetic Management of Early-Onset Scoliosis
Published in Alaaeldin (Alaa) Azmi Ahmad, Aakash Agarwal, Early-Onset Scoliosis, 2021
Damarla Haritha, Souvik Maitra
Musculoskeletal System: In patients with congenital myopathies, there can be weakness of the muscles in general and bulbar involvement that leads to frequent aspirations, complicating the perioperative course. Duchenne muscular dystrophy is an X-linked recessive disorder caused by a defect in the gene coding ‘dystrophin’, a muscle protein [22]. The patient will be restricted to a wheelchair by 8–10 years of age, and the expected life span is 15–16 years. It is associated with cardiomyopathy and fatal arrhythmias. The corrective scoliosis surgery helps to improve nursing and quality of life in such patients and should be done at a lower Cobb angle to prevent progression of the curve and appearance of cardiomyopathy [23].
The locomotor system
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Mutations in the dystrophin gene on the short arm of chromosome X cause both disorders and its protein product, dystrophin, has been characterized. Normal dystrophin is a large molecular component of the sarcolemmal plasma membrane. When the gene is mutated, dystrophin is either absent or undetectable as in Duchenne dystrophy, or of abnormal constitution as in Becker dystrophy. The clinical phenotypes correlate well with the quantity and quality of dystrophin (Figure 13.49). In Duchenne dystrophy two-thirds of mutations are inherited from the mother. The remaining third of mutations are new mutations, reflecting the large size of the gene, which contains several hot spots. Most patients with Duchenne dystrophy have a deletion or duplication resulting in the truncation of translation and a small unstable molecule. The muscle biopsy shows a characteristic appearance with variation in muscle fibre size, some showing necrosis. In the later stages muscle is replaced by fat and fibrous tissue (Figure 13.50). Diagnosis can now be made by sequencing of DNA to identify mutation of the dystrophin gene. This is done on a blood sample.
Next steps for the optimization of exon therapy for Duchenne muscular dystrophy
Published in Expert Opinion on Biological Therapy, 2023
Galina Filonova, Annemieke Aartsma-Rus
Duchenne muscular dystrophy (DMD) is an X-linked inherited muscle disorder, caused by an absence of a functional dystrophin protein. Dystrophin is a crucial protein for the maintenance of muscle fiber stability. It links the intracellular actin cytoskeleton and extracellular matrix through N-terminal and C-terminal domains, respectively, thus forming the dystrophin protein complex (DPC). The DPC functions as a structural complex to mechanically stabilize the muscle membrane, and as a signaling complex. Due to the absence of dystrophin, the DPC cannot properly form. Consequently, muscle fibers of DMD patients are susceptible to damage during contraction, leading to chronic inflammation, impaired regeneration, and fibrosis formation [1]. DMD is primarily diagnosed in early childhood when clinical signs and symptoms such as muscle weakness, clumsiness, and difficulties with climbing and walking occur. Further testing for serum creatine kinase level, which is increased in DMD patients, and testing for DMD gene mutations confirm a suspected diagnosis of DMD. The disease progresses over the lifespan gradually leading at first to skeletal muscle dysfunction and loss of ambulation, next to the loss of arm function, dysfunction of respiratory and cardiac muscles, and death usually in the 3rd to 4th decade [2].
Proteomic profiling of carbonic anhydrase CA3 in skeletal muscle
Published in Expert Review of Proteomics, 2021
Paul Dowling, Stephen Gargan, Margit Zweyer, Hemmen Sabir, Dieter Swandulla, Kay Ohlendieck
The muscular dystrophies are a large group of inherited disorders that primarily affect skeletal muscles [114]. X-linked muscular dystrophies are due to mutations in the DMD gene that encodes a variety of tissue-specific isoforms of the protein named dystrophin. Loss of the full-length dystrophin isoform Dp427-M causes the Duchenne type of muscular dystrophy, which is a highly progressive muscle wasting disorder of early childhood [115]. Dystrophin exists in skeletal muscles in a tight linkage with several sarcolemmal glycoproteins [116]. The core dystrophin-glycoprotein complex interacts with the basal lamina on the outside of muscle fibers and the actin membrane cytoskeleton on the inside of contractile cells forming a supramolecular membrane assembly. The dystrophin complex was shown to be involved in the integration of fiber stability, the transmission of lateral force to the extracellular matrix, the organization of the cytoskeletal network and cellular signaling events in the peripheral membrane system of skeletal muscle fibers [116].
Soluble guanylate cyclase stimulators and their potential use: a patent review
Published in Expert Opinion on Therapeutic Patents, 2021
Peter Sandner, Alexandros Vakalopoulos, Michael G. Hahn, Johannes-Peter Stasch, Markus Follmann
DMD is a monogenetic disorder affecting 1 in 5000 boys. The lack of dystrophin leads to progressive muscle wasting, physical and cognitive disability, and substantially reduced life expectancy mainly due to cardio-respiratory failure. Like in CF and despite multiple efforts for cell- and gene-based therapies there is still no cure for DMD. It was shown that sGC modulation improves diaphragm function in mice with muscular dystrophy (mdx-mice), suggesting beneficial effects on respiratory function in DMD (WO2014190250) [73]. In addition, sGC modulation increased the physical activity and also heart function, as assessed by cardiac hemodynamics. In addition, it was demonstrated that sGC agonists could increase muscular blood flow in mdx mice (WO2015106268) [74]. Osteogenesis Imperfecta (OI)