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：
05454468
负责人：
NAKAZAWA Mitsuru
金额：
$ 4.22万
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：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

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 nature, 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 project, we have performed molecular genetic researches for RP,especially studies for detecting gene abnormalities in Japanese patients with RP.As the first project, we searched for mutations within the rhodopsin gene and the peripherin/RDS gene in Japanese patients with autosomal dominant RP (adRP) and allied deseases. We employed nonradiosotopic SSCP method that had been established in our past research project (Grant-in-Aid for Scientific Research, B-O354411) to detect putative mutations. To date, we have detected a point mutation in codon 347 (Pro347Leu) in the rhodopsin gene. We also have identified 5 different mutations in the peripherin/RDS gene, and they were Asn244Lys, Asn244His, Tyr184Ser, Arg172Trp, and Val200Glu, respectively. Studies for genotype-phenotype correlation have revealed that Asn244Lys causes rod-cone dystrophy, while Asn244His, Tyr184Ser, and Val200Glu cause cone-rod dystrophy, and Arg172Trp is responsible for macular dystrophy.As the second part, we have perfoumed linkage analysis for a large family with adRP using several genetic markers. As a result, a positive linkage was obtained between the desease gene and the locus on chromosome 19q (D19S180, Zmax=5.110). Further molecular genetic study will clarify a candidate gene for this locus.

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。这是日本成年人中第三大常见的法定失明原因（12%）。由于其遗传性，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，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式。在本研究项目中我们对RP进行了分子遗传学研究，特别是检测日本RP患者基因异常的研究。作为第一个项目，我们在日本RP患者中寻找视紫红质基因和外周蛋白/RDS基因内的突变。常染色体显性 RP (adRP) 和相关疾病。我们采用了我们过去的研究项目（科学研究资助，B-O354411）中建立的非放射性 SSCP 方法来检测假定的突变。迄今为止，我们已经检测到视紫红质基因中密码子 347 (Pro347Leu) 的点突变。我们还鉴定了外周蛋白/RDS基因中的5个不同突变，它们分别是Asn244Lys、Asn244His、Tyr184Ser、Arg172Trp和Val200Glu。基因型-表型相关性研究表明，Asn244Lys 导致视杆细胞营养不良，Asn244His、Tyr184Ser 和 Val200Glu 导致视锥细胞营养不良，Arg172Trp 导致黄斑营养不良。作为第二部分，我们对大量数据进行了连锁分析。使用多个遗传标记的 adRP 家族。结果，疾病基因与19q染色体上的基因座(D19S180，Zmax＝5.110)之间获得正连锁。进一步的分子遗传学研究将阐明该基因座的候选基因。