GENETIC BASIS FOR THE SEVERITY OF RETINITIS PIGMENTOSA

色素性视网膜炎严重程度的遗传基础

• 批准号: 2888546
• 负责人: THADDEUS P DRYJA
• 金额: $ 36.06万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2888546
• 关键词: autosomal dominant trait; clinical research; electroretinography; family genetics; gene mutation; genetic markers; genetic polymorphism; human subject; linkage mapping; pathologic process; phenotype; retinitis pigmentosa; rhodopsin; visual fields

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.

描述：（改编自研究者摘要）：患者 色素性视网膜炎会导致视力进行性丧失并经历严重的 通常到中年时就会出现视力障碍或失明。 该病是由于 视杆细胞和视锥细胞感光细胞的遗传性变性 视网膜。 在美国，大约 25% 的病例属于主导模式 传播的原因是视紫红质基因的突变。 最 仅称为 Pro23His 的普遍突变就占了约 9% 占主导地位的案例。 在视紫红质突变的患者中，尤其是 在具有 Pro23His 突变的人中，申请人观察到显着的 通过视觉测量视网膜变性严重程度的变化 场面积或视网膜电图 (ERG)。 申请人提出 研究旨在确定这种严重程度的变化程度， 其延伸超过2个数量级，是由于一个或多个的作用 更多修饰基因。 视紫质基因将被评估为候选基因 修饰基因。 患有 Pro23His 突变的一对受影响的兄弟姐妹将 进行分析以检验变体“野生型”视紫红质的假设 从未受影响的父母遗传的等位基因可能会调节疾病的严重程度 疾病。 如果数据表明视紫红质等位基因不太可能发生改变 严重程度，将使用微卫星标记进行连锁研究 试图识别可能携带修饰基因的染色体区域。 了解色素性视网膜炎严重程度的变化可以 对受影响的患者产生重大影响，因为如果能够以某种方式 将所有病例转换为最不严重的类型，将会有大量的 减少由疾病引起的视力障碍。