Muscular Duchenne

Duchenne muscular dystrophy gene (at 2.4 megabases, the largest known gene in any organism)... 

LGMD, limb girdle muscular dystrophy DMD, Duchenne muscular dystrophies BMD, Becker muscular dystrophies... 

Figure 1. Immunofluorescent labeling of dystrophin in the Xp21 muscular dystrophies. In normal muscle, clear uniform labeling is present at the membrane of each muscle fiber. In Becker muscular dystrophy (BMD), there is inter- and intrafiber variation in labeling intensity. In Duchenne muscular dystrophy (DMD), most fibers are devoid of labeling (note, however, that in most biopsies occasional fibers exhibit weak labeling). In the biopsy from a manifesting carrier, some fibers show normal labeling and others are negative. In the former, the normal X-chromosome is active while in the latter the abnormal X-chromosome is active.

Figure 2. Erb s illustration of the pathology of muscle from patients with Duchenne muscular dystrophy. Note the variation in muscle fiber diameter, fiber-splitting, deposition of fat and infiltration of connective tissue. Drawing from several biopsies produced during final decade of 19th century. 

Emery, A.E.H. (1993). Duchenne Muscular Dystrophy. Oxford University Press. Oxford. 

Hoffrnan, E.P., Kunkel, L.M. (1989). Dystrophin abnormalities in Duchenne/Becker muscular dystrophy. Neuron 2, 1019-1029. 

MUTATIONS IN THE GENE ENCODING DYSTROPHIN CAUSE DUCHENNE MUSCULAR DYSTROPHY... 

Dystrophin Attached to plasma-lemma Deficient in Duchenne muscular dystrophy. Mutations of its gene can also cause dilated cardiomyopathy. 

Figure 49-11. Summary of the causation of Duchenne muscular dystrophy (MIM 310200).

Duchenne muscular dystrophy. Mutations in the genes encoding some of the components of the sarcoglycan complex shown in Figure 49-12 are responsible for limb-girdle and certain other congenital forms of muscular dystrophy. 

Duchenne-type muscular dystrophy is due to mutations in the gene, located on the X chromosome, encoding the protein dystrophin. 

Detection of specific cytogenetic abnormalities For instance, a small deletion of band Xp21.2 was important in cloning the gene involved in Duchenne muscular dystrophy. 

Nineteen women underwent amniocentesis for the determination of fetal sex. Several different X-llnked abnormalities constituted the Indications for this procedure, and these Included hemophilia A, hemophilia B, Duchenne muscular dystrophy, optic albinism, X-llnked mental retardation, the Lesch-Nyhan syndrome (due to dlflclency of hypoxanthlne-guanlne phosphorlbosyltransferase, and Fabry s disease (due to deficiency of an a-galact-osldase). Fourteen of the fetuses were male. Including one which turned out to be a set of twins, and most of the male pregnancies were terminated. The sex determination being carried out for Fabry s disease Is of particular Interest, since In this case It was desired to find out whether the fetus was a female. 

Toop, J. and Emery, A. E. H. "Muscle Histology In Fetuses at Risk for Duchenne Muscular Dystrophy". Clin. Genet., (1974), 5, 230-233. 

Foxley, A., Edwards, R.H.T. and Jackson, M.J. (1991). Enhanced lipid peroxidation in Duchenne muscular dystrophy may be secondary to muscle damage. Biochem. Soc. Trans. 19, 1805. 

Griffiths, RD., Cady, E.B., Edwards, RH.T. and Wilkie, D.R (1985). Muscle energy metabolism in Duchenne muscular... 

Higuchi, M., Cartier, L.J., Chen, M. and HoUoszy, J.O. (1985). Superoxide dismutase and catalase in skeletal muscle adaptive response to exercise. J. Gerontol. 40, 281-286. Hunter, M.I.S., Brzeski, M.S. and de Vane, P.J. (1981). Superoxide dismutase, glutathione peroxidase and thiobarbi-turic acid-reactive compounds in erythrocytes in Duchenne muscular dystrophy. Clin. Chim. Acta 115, 93-98. 

Jackson, M.J., Kaiser, K., Brooke, M.H. and Edwards, RH.T. (1991). Glutathione depletion during experimental damage to skeletal muscle and its relevance to Duchenne muscular dystrophy. Clin. Sci. 80, 559-564. 

RFLPs are often a reflection of individual genetic diversity and are not related to a clinical phenotype, but occasionally they can be diagnostic of an inherited disease. This technique is relatively new yet, it has been applied to the prenatal detection of sickle cell anemia, thalassemia, phenylketonuria, a,-antitrypsin deficiency, Huntington s chorea, Duchenne muscular dystrophy, hemophilia A and B, cystic fibrosis, and several other, diseases. 

Reverse genetics has been applied to diseases such as Duchenne muscular dystrophy and cystic fibrosis, in which the responsible enzymes are unknown and the disease results from a significant deletion. By combining RFLP analysis with cytogenetics, it has been possible to increasingly narrow the location of the defective genes to small regions on the affected chromosomes. 

Enteric Myopathies. The familial types include the dominant type 1 [150], the recessive type 2 with ophthalmoplegia [151] and the recessive type 3 [116]. The sporadic types include muscular dystrophies [152] including myotonic dystrophy [153] and Duchenne s dystrophy. Dysmotility has been associated with all these diseases. 

The clinical picture in male children can closely resemble Duchenne-type muscular dystrophy in adults, it mimics limb-girdle dystrophy or polymyositis. The early and severe involvement of respiratory muscles in most patients with AMD is a distinctive clinical clue. Respiratory failure and pulmonary infection are the most common causes of death. 

Duchenne muscular dystrophy dimethyl formamide 5,5-dimethyl-1 -pyrroline-1 -oxide deoxynucleic acid diphenylene iodonium endothelium-derived relaxing factor epidermal growth factor early growth phase response gene ethyleneglycol- bis- (p- aminoethyl)-N,N,N, N -tetraacetic acid... 

Duchenne and Becker Muscular Dystrophy Current Diagnostics. 55... 

Duchenne and Becker muscular dystrophies (DMD and BMD) are X-linked, allelic, neuromuscular diseases. DMD/BMD are characterized by progressive muscular weakness and degeneration of skeletal muscle. DMD is the most common recessive lethal disease, with an incidence of approximately 1 in 3500 newborns, and according to estimates, one-third of the cases are linked with new mutations (M3). Clinical symptoms of the disease appear earlier, by 2 to 3 years of age, in the form of retarded motor development. Progressive symptomatic children show weakness and wasting of muscle and are usually wheelchair bound approximately by the age of 11-12 years. It has been reported that most patients die at about the age of 20 due to pneumonia, which is related to chronic respiratory insufficiency. BMD—being the rarer allelic disorder—has a milder clinical course with slower disease progression. The BMD-affected patients usually survive beyond the age of 30. 

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