Molecular Biological Research for Retinitis Pigmentosa

视网膜色素变性是一组遗传性疾病，表现为双眼视力和视野进行性丧失，并伴有夜盲。这是导致日本成年人法律失明的第三大原因(12%)。由于RP的遗传性，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，从而设计出比目前更好或更有效的治疗方案。在本研究中，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，用于检测日本RP患者的基因异常。首先，我们寻找了视紫红质基因的突变，该基因已被认为是RP的候选基因。我们使用非放射性同位素SSCP来检测点突变或多态。到目前为止，我们已经在一个患有ADRP和多态…的家庭中检测到了第347密码子(Pro347Leu)的点突变在40个ADRP家系中，外显子1、4、5的短信频率较高。有研究表明，日本ADRP患者的视紫红质基因突变频率(2.5%)远低于欧美人群报道的视紫红质突变频率(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在日本患者中是否存在突变。使用与视紫红质基因相同的策略，我们已经检测到外周蛋白/RDS基因在adrp家族中的一个点突变(Asn144Lys)。由于该突变(Asn144Lys)以前未见报道，我们分析了该突变的基因-表型关系，以阐明该突变对RP的临床特征的贡献。该家系的临床特征包括缓慢进行性的视杆-视锥细胞营养不良，甚至在RP早期视杆和视锥细胞的ERG反应严重受损，以及30‘S晚期以后的牛眼黄斑病变。

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