Dystrophin gene mutations

Amalfitano, A., Rafael, J.A., and Chamberlain, J.S., 1997, Structure and mutation of the dystrophin gene. In Dystrophin Gene, Protein and Cell Biology (S. Brown and J.A. Lucy, eds) Cambridge University Press, Cambridge, UK, pp 1-26. 

Lenk, U., Hanke, R., Thiele, H., and Speer, A., 1993, Point mutations at the carboxy terminus of the human dystrophin gene implications for an association with mental retardation in DMD patients, Hum Mol Genet, 2, pp 1877-1881. 

In Duchenne muscular dystrophy the most common mutations are deletions of portions of the extremely large (> 2 megabases) dystrophin gene (17-19). These deletions frequently contain RFLP sites leading to a loss of the RFLP band associated with the mutant X chromosome contributed by a carrier female to her son or daughter (Fig. 7). 

Since alterations in global DNA methylation are implicated in various pathobio-logical processes, a gradient IPC-ESI-MS/MS method with a volatile IPR was used to determine cytosine and 5-methylcytosine in DNA quantification relied on stable isotope dilution [58], Muscular dystrophies caused by various mutations in the dystrophin gene are amenable to easier prenatal diagnosis via a multiplex polymerase chain reaction (PCR)/IPC assay [59]. Some guidelines for the analysis of genomic DNA by IPC-ESl-MS can be found in Reference 60. 

Roberts, R.G., Bobrow, M., and Bently, D.R. (1992). Point mutations in the dystrophin gene. Proc. Natl. Acad. Sci. USA... 

Feng J, Yan J, Buzin CH, Sommer SS, Towbin JA. Comprehensive mutation scanning of the dystrophin gene in patients with nonsyndromic X-linked dilated cardiomyopathy. J Am CoU Cardiol 2002 40 1120-4. 

Milasin J, Muntoni F, Severini GM, Bartoloni L, Vatta M, Krajinovic M, et al. A point mutation in the 5 splice site of the dystrophin gene first intron responsible for X-linked dilate cardiomyopathy. Hum Molec Genet 1996 5 73-9. 

Patients with Duchenne muscular dystrophy are deficient not only in dystrophin but also in the dystro-glycan and sarcoglycan proteins. " " Evidently, dystrophin is needed for formation of the complex which plays an essential role in muscle. In both types of X-linked muscular dystrophy there are individuals with a wide range of point mutations, frame-shift mutations, and deletions in the dystrophin gene. ... 

Duchenne s muscular dystrophy is 1)) caused by the absence of the pro-oO / tein dystrophin, which is a structural protein located in the sarcolemma. Dystrophin is required to maintain the integrity of the sarcolemma, and when absent leads to a loss of muscle function, caused by breakdown of the sarcolemma. The gene is X-linked, and mutations that lead to Duchenne s muscular dystrophy generally result from large deletions of the gene, such that dystrophin is absent from the membrane. Becker s muscular dystrophy, a milder form of disease, is caused by point mutations in the dystrophin gene. In Becker s muscular dystrophy, dystrophin is present in the sarcolemma, but in a mutated form. 

Real-time detection was also used for an isothermal amplification procedure termed nucleic acid sequence-based amplification, for the detection of artificial human papilloma virus sequences in SiHa cells. This method was not applied to real samples, but demonstrates the clinical applicability of additional microchip enzymatic amplification methods. Not all clinical microchip PCR amplifications looked for infectious agents, however. Cheng et al. showed a microchip PCR method for multiplex amplifications of dystrophin gene fragments for the detection of mutations associated with muscular dystrophy. 

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. 

Another type of cardiomyopathy is termed dilated cardiomyopathy. Mutations in the genes encoding dystrophin, muscle LIM protein (so called because it was found to contain a cysteine-tich domain originally detected in three proteins Lin-II, Isl-1, and Mec-3), and the cyclic response-element binding ptotein (CREB) have been implicated in the causation of this condition. The first two proteins help organize the conttactile ap-params of cardiac muscle cells, and CREB is involved... 

Figure 49-13. Simplified scheme of the causation of familial hypertrophic cardiomyopathy (MIM 192600) due to mutations in the gene encoding fi-myosin heavy chain. Mutations in genes encoding other proteins, such as the troponins, tropomyosin, and cardiac myosin-binding protein C can also cause this condition. Mutations in genes encoding yet other proteins (eg, dystrophin) are involved in the causation of dilated cardiomyopathy.

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

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