|Budget Amount *help
¥6,200,000 (Direct Cost : ¥6,200,000)
Fiscal Year 1992 : ¥2,600,000 (Direct Cost : ¥2,600,000)
Fiscal Year 1991 : ¥3,600,000 (Direct Cost : ¥3,600,000)
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
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