Molecular Biological Research for Retinitis Pigmentosa

色素性视网膜炎的分子生物学研究

基本信息

批准号：
03454411
负责人：
NAKAZAWA Mitsuru
金额：
$ 3.97万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454411/
关键词：
Retinitis Pigmentosa Autosomal Dominant Retinitis Pigmentosa Rhodopsin Peripherin RDS SSCP MEKA RDS 網膜特異的蛋白質ロドプシン遺伝子 MEKA蛋白質 PCR法 SSCP法

项目摘要

Retinitis pigmentosa (RP) is a group of hereditary disorders which show bilateral progressive loss of visual acuity and visual field, and night blindness. This is the third most frequent cause (12%) of legal blindness among adult Japanese population. Because of its hereditary natures, researches at the level of genes should be necessary to obtain better understandings of the mechanism of pathogenesis of RP, so that we can specifically design better or more effective modalities of treatment than what we have now.In this study, we have performed molecular genetic researches for RP, especially so- called candidate gene approaches for detecting gene abnormalities in Japanese patients population with RP.Firstly, we searched mutations within the rhodopsin gene, which has been known to be a candidate gene for RP. We employed nonradioisotopic SSCP to detect point mutations or polymorphisms. To date, we have detected a point mutation in codon 347 (Pro347Leu) in a family with ADRP and polymorphi … More sms in or around Exons 1,4 and 5 among 40 families with ADRP. It has been suggested that the frequency of the rhodopsin mutation among Japanese patient popuklation with ADRP (2.5%) is much lower than that reported in American and European population (12-30%).Secondly, we analysed peripherin/RDS gene and MEKA protein gene to answer whether patients with mutations in these genes can be seen in Japanese patients pophlation or not. Using the same strategy as the rhodopsin gene, we have detected a point mutation (Asn144Lys)within the peripherin/RDS gene ina family with ADRP. Because the mutation (Asn144Lys) has not been reported before, we analysed the genotype- phenotype relationship in order to clarify the contribution of this mutation to clinical features of RP.The characteristics of clinical features appeared in this family include slowly progressive nature of rod-cone dystrophy, severely damages of ERG responses in both rod and cone even at the early stage of RP, and bull's eye maculopathy after late 30's. Less

色素性视网膜炎 (RP) 是一组遗传性疾病，表现为双侧视力和视野进行性丧失以及夜盲症，由于其遗传性，这是导致日本成年人失明的第三大常见原因 (12%)。从本质上讲，为了更好地了解 RP 的发病机制，有必要进行基因水平的研究，以便我们能够有针对性地设计出比现有技术更好或更有效的治疗方案。在这项研究中，我们对 RP 进行了分子遗传学研究，特别是用于检测日本 RP 患者群体中基因异常的所谓候选基因方法。首先，我们搜索了视紫红质基因内的突变，该基因已知是 RP 的候选基因。 SSCP 检测点突变或多态性迄今为止，我们在一个具有 ADRP 和多态性的家族中检测到密码子 347 (Pro347Leu) 的点突变。或在 40 个 ADRP 家族中的外显子 1,4 和 5 附近。有人认为，日本 ADRP 患者群体中视紫红质突变的频率 (2.5%) 远低于美国和欧洲人群 (12-30) 的报道。 %).其次，我们使用相同的策略分析了外周蛋白/RDS基因和MEKA蛋白基因，以回答这些基因突变的患者是否可以在日本患者中看到。作为视紫红质基因，我们在ADRP家族的外周蛋白/RDS基因中检测到了点突变（Asn144Lys），因为该突变（Asn144Lys）以前没有报道过，我们分析了基因型与现象的关系，以澄清其贡献。该突变与 RP 的临床特征有关。该家族出现的临床特征包括视杆细胞营养不良的缓慢进行性、两者 ERG 反应的严重损害即使在 RP 的早期阶段，也会出现视杆细胞和视锥细胞，30 岁后期后也会出现牛眼黄斑病变。