GENETIC BASIS FOR THE SEVERITY OF RETINITIS PIGMENTOSA

描述：（改编自研究者摘要）：患有

DESCRIPTION: (Adapted from the Investigator's Abstract): Patients with retinitis pigmentosa have a progressive loss of vision and experience severe visual handicap or blindness usually by middle age. The disease is due to hereditary degeneration of both rod and cone photoreceptor cells in the retina. In the United States about 25 percent of cases with a dominant mode of transmission are due to a mutation in the rhodopsin gene. The most prevalent mutation, called Pro23His, alone accounts for about 9 percent of dominant cases. Among patients with rhodopsin mutations and especially among those with the Pro23His mutation, the applicants have observed marked variation in the severity of retinal degeneration as measured by visual field area or by the electroretinogram (ERG). The applicants propose studies aimed at determining the degree to which this variation in severity, which extends over 2 orders of magnitude, is due to the action of one or more modifier genes. The rhodopsin gene will be evaluated as a candidate modifier gene. Pairs of affected siblings with the Pro23His mutation will be analyzed to test the hypothesis that variant "wild-type" rhodopsin alleles inherited from unaffected parents might modulate the severity of disease. If the data indicate that rhodopsin alleles are unlikely to modify severity, a linkage study using microsatellite markers will be undertaken in an attempt to identify chromosomal regions likely to carry modifier genes. Understanding the variation in the severity of retinitis pigmentosa could have a significant impact on affected patients, since if one could somehow convert all cases to the least severe type there would be a substantial reduction in the visual handicap caused by the disease.