GENETIC BASIS FOR THE SEVERITY OF RETINITIS PIGMENTOSA

描述：(改编自《调查者摘要》)：患有 视网膜色素性视网膜炎是一种进行性失明，症状严重。 通常在中年时有视力障碍或失明。这种疾病是由于 视杆细胞和视锥细胞的遗传性变性 视网膜。在美国，约25%的案件以主导模式 传播的主要原因是视紫红质基因的突变。最多的 仅名为Pro23His的流行突变就占到了约9% 显性案例。在视紫红质突变患者中，尤其是 在携带Pro23His突变的人中，申请者观察到明显的 视力测量视网膜变性严重程度的变化 视野面积或视网膜电信号(ERG)。申请者提议 旨在确定这种严重性差异的程度的研究， 它延伸了两个数量级，是由于一个或两个数量级的 更多的修饰基因。视紫红质基因将作为候选基因进行评估 修饰基因。带有Pro23His突变的一对受影响的兄弟姐妹将 被分析以检验变种“野生型”视紫红质的假设 从未受影响的父母那里继承的等位基因可能调节了 疾病。如果数据表明视紫红质等位基因不太可能改变 严重程度，使用微卫星标记的连锁研究将在#年进行。 试图确定可能携带修饰基因的染色体区域。 了解视网膜色素变性的严重程度的变化可以 对受影响的患者有重大影响，因为如果一个人能以某种方式 将所有病例转换为最轻类型将有大量的 减少由这种疾病引起的视力障碍。

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.