Disease genetic, point mutations

Heritable and spontaneous genetic disorders represent additional applications for therapeutic ribozymes targeting cellular genes. These include the beta-amyloid peptide precursor mRNA involved in Alzheimer s disease (Currie et al., 1997 Dolzhanskaya et al., 2000), and an autosomal-dominant point mutation in the rhodopsin mRNA that gives rise to photoreceptor degeneration and retinitis pigmentosa (Hauswirth and Lewin, 2000 LaVail et al., 2000). 

Although DNA mutations in nuclear DNA may cause mitochondrial dysfunction, the majority of genetically defined mitochondrial diseases are caused by mutations in mtDNA (M15, PI, S4). Point mutations and deletions of mtDNA have been reported to be associated with or responsible for mitochondrial myopathies and/or encephalomyopathies (M15, PI, S4). Patients with such diseases usually manifest major clinical symptoms early in life and at a later stage may develop additional multisystem disorders such as encephalopathy and/or peripheral neuropathy. Most of the mitochondrial myopathies occur sporadically and are often caused by large-scale mtDNA deletions (PI). However, there are several reports on maternally inherited mitochondrial myopathy and familial mitochondrial myopathy. These patients usually harbor a specific mtDNA mutation and often exhibit defects in NADH-CoQ reductase and/or cytochrome c oxidase. 

Li DY, Toland AE, Boak BB, Atkinson DL, Ensing GJ, Morris CA, Keating MT. Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis. Hum Mol Genet 1997 6(7) 1021-1028. 

Yes, a number of human diseases are caused by point mutations in the promoter regions of important genes. For example, /3-thalassemia is a genetic disease in which mutations in the promoter of the /3-globin gene result in reduced production of this protein and subsequent anemia. The mutation is usually associated with a reduction in the binding affinity of the promoter for a positive transcription factor. 

Turner, Z., Lund, C., Tolshave, J., Vural, B., Tonnesen, T., and Horn, N. (1997). Identification of point mutations in 41 unreleated patients affected with Menkes disease. Am. J. Hum. Genet. 60, 63-71. 

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