GENETIC BASIS FOR THE SEVERITY OF RETINITIS PIGMENTOSA

描述：（改编自研究者摘要）：患者 色素性视网膜炎具有进行性视力丧失， 视力障碍或失明，通常在中年。 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，大约25%的显性模式病例 都是由于视紫红质基因的突变。 最 一种叫做Pro23His的流行突变，仅占人类基因组的9%。 占主导地位的案件。 在视紫红质突变的患者中， 在具有Pro23His突变的那些人中，申请人观察到显著的 通过视觉测量的视网膜变性严重程度的变化 场区或通过视网膜电图（ERG）。 申请人建议 旨在确定这种严重程度变化的研究， 其延伸超过2个数量级，是由于一个或 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 携带Pro23His突变的受影响兄弟姐妹将 进行分析，以检验变异的“野生型”视紫红质 从未受影响的父母遗传的等位基因可能会调节 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，将进行使用微卫星标记的连锁研究， 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严重程度的变化， 对受影响的患者有重大影响，因为如果一个人可以以某种方式 将所有病例转换为最不严重的类型， 减少由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.