Point mutations retinitis pigmentosa

O Point mutations causing serious diseases. P23H is a frequent cause of retinitis pigmentosa. Mutations G90D and A292E cause congenital night blindness. 

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). 

Theoretically, inverse agonists may be useful agents for the treatment of disease symptoms caused by constitutive receptor activity. Covalent modifications of the receptor protein, pathological increase in receptor or G protein densities, or inherited or somatic point mutations may lead to increased constitutive receptor activity. For example, certain inherited point mutations in rhodopsin have been shown to cause retinitis pigmentosa. The involvement of inherited, constitutively activating receptor point mutations has also been demonstrated in certain forms of hyperthyroidism, in male precocious puberty, and in Jansen-type metaphyseal chondrodysplasia [8]. Constitutive G protein activity may also be an important factor in autoimmune diseases [9]. 

Dryja TP, Mcgee TL, Reichei E, Hahn LB, Cowley GS, et al. 1990b. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343 364-366. 

An autosomal dominant form of the disease arises from deletions or poinf mufations in the rhodopsin gene. In the United States 15% of cases arise from the mutation P23H. By 1996 70 point mutations that cause retinitis pigmentosa had been discovered These mutations are foimd in all three... 

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