Muscular dystrophy 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. 

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. 

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. 

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. 

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... 

Molecular diagnostics approaches to carrier status for Duchenne muscular dystrophy are based on the discovery of the presence of a deletion in the gene for dystrophin. Sometimes, the testing approach provides a probability or likelihood estimate of an individual being a carrier (e.g., the use of indirect or linkage analysis for DMD when a deletion is not detectable), rather than clear documen-... 

K3. Koenig, M., Hoffman, E. P., Bertelson, C. J., Monaco, A. P., Freener, C., and Kunkel, L. M., Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell (Cambridge. MA) 50, 509-517 (1987). 

M3. Moser, H., Duchenne muscular dystrophy Pathogenetic aspects and genetic prevention. Hum. Genet. 66, 17—40 (1984). 

Zn-binding domain, present in CBP/p300 and Dystrophin. In Dystrophin, domain is implicated in Calmodulin binding. Mis-sense mutation of conserved cysteine correlates with Duchenne muscular dystrophy. 

Exhibits 2.2,2.3, and 2.4 provide examples of genetic causes of diseases, for example, cancer, sickle cell anemia, and cystic fibrosis. It should be noted that although some of these diseases are the result of mutations in a single gene (including Huntington s disease and Duchenne muscular dystrophy), most are due to the influence of multiple genes. 

The clinical progression of Becker muscular dystrophy is typically much slower than that of Duchenne muscular dystrophy. This is usually the result of... 

The incidence of Duchenne muscular dystrophy in North America is about 1/3,000 males. On the basis for this figure, what is the gene frequency of this X-linked recessive mutation ... 

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