Molecular Biological Research for Retinitis Pigmentosa

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和夜盲症。这是日本成年人法定失明的第三大常见原因（12%）。由于其遗传特性，有必要在基因水平上进行研究，以更好地了解RP的发病机制，以便我们能够针对性地设计出比现有治疗方法更好或更有效的治疗方法。在这项研究中，我们进行了RP的分子遗传学研究，特别是所谓的候选基因方法来检测日本RP患者群体的基因异常。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。我们采用非放射性同位素SSCP检测点突变或多态性。迄今为止，我们在一个ADRP家族中检测到密码子347 （Pro347Leu）点突变，并在40个ADRP家族中检测到多态性。有研究表明，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%）。其次，我们分析了外周蛋白/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人群中看到。使用与视紫红质基因相同的策略，我们在ADRP家族的外周蛋白/RDS基因中检测到一个点突变（Asn144Lys）。由于该突变（Asn144Lys）之前未被报道，我们分析了基因型-表型关系，以阐明该突变对RP临床特征的贡献。该家族的临床特征表现为杆状体和锥体营养不良的缓慢进行性，即使在RP的早期，杆状体和锥体的ERG反应也严重受损，30岁以后出现牛眼黄斑病变。少

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