Mutations clinical applications

In this chapter, we review some of the practical clinical applications of genetic research. Once a gene is identified, it becomes feasible to diagnose the associate genetic disease in at-risk individuals. In addition, gene therapy, the correction of mutations in cells, becomes a possibility. 

This volume continues our objective of expanding the intellectual horizon of clinical chemistry. Included are chapters on Clinical Applications of Cytokine Assays Diagnosis and Treatment of Acute Pancreatitis Mitochondrial Mutations and Mitochondrial Diseases Pathobiochemistry of Nephrotic Syndrome Total Antioxidant Capacity Autoantibodies to dsDNA, Ro/SSA, and LaSSB in Systemic Lupus Erythematosis and Lymphoid Malignancies and Immunosuppressive Analysis. The meld of analytical, anatomical, subcellular, and molecular sciences represented by these subjects will continue to evolve and expand. Clinical chemistry is a vibrant and vital profession. Future volumes, their editors, and their contributors will undoubtedly be an important part of the practice and science of clinical chemistry. 

Bilirubin oxidase, purified and characterized from the fungus Myrothecium verrucaria, has a strong amino acid sequence homology with the other blue copper oxidases and point mutations studies on the supposed copper binding residues have confirmed its identity as a member of the enzymatic family.In vitro, BO couples 02-reduction to the oxidation of bilirubin to biliverdin. This catalytic activity has found clinical application in the diagnosis and treatment of jaundice and hyperbilirubinemia. 

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. 

Mutation of certain amino acids results in rhodopsins that are also constitutively active, that is, the protein can activate transducin in the absence of light [35-37]. Rim and Oprian [38] have shown that rhodopsin mutants that are constitutively active are also phosphorylated by rhodopsin kinase. These results are in agreement with the results on the active opsin complexes discussed above. These mutants disrupt the salt bridge between lysine 296 and glutamate 113 [35-37] and therefore prevent the inactive conformation of the rhodopsin state. These studies have important clinical applications as it has been found that several of the mutations of rhodopsin found in individuals with retinal degenerative disorders result in constitutively active pigments [39]. 

Clinical applications of photosensitization hold considerable promise. Unlike alternative therapies, such as ionizing radiation, photodynamic therapy can be repeated with no known limits. It poses considerably less risk to administering personnel. The photon energy is not sufficient to produce DNA damage directly, and most photosensitizers in use do not penetrate to the nucleus or interact with nuclear DNA, so mutation is not as significant a concern. With the current protocols, an apoptotic response appears to be dominant, with no inflammatory response at the treatment site. 

Sequence changes, including polymorphisms and mutations, are clinically important. In addition to medicolegal applications, they can also be indicators for susceptibility and prognosis for different malignancies [52]. KLK3 is the most extensively studied kallikrein in this respect. Comparison of the... 

There is a vast array of techniques that are currently being used to look for mutations for clinical molecular diagnostic use. The following overview of methods describes some of the most common techniques to detect recurrent mutations used in many diagnostic laboratories. As detection of unique mutations is not of relevance to pharmacogenetic applications, this topic will not be discussed in this chapter. 

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