Molecular Genetic Analysis of Retinitis Pigmentosa

为了研究抑制蛋白基因突变是否不仅是一种先天性静止性夜盲症Oguchi病的原因，也是一种进行性视网膜变性视网膜色素变性的原因，我们继续对抑制蛋白基因进行突变筛选，并进一步分析基因型与表型的关系。结果，我们在3例常染色体隐性视网膜色素变性患者中发现了与Oguchi病患者相同的抑制蛋白基因（ll47delA）突变。3例患者中，2例眼底表现为典型的视网膜色素性变性，1例表现为中枢性色素性视网膜炎，伴周围金黄色眼底反射。在视网膜电图中，所有3例患者均表现为a波和b波减少，但标准ERG未完全减少，并且他们通常表现为波减少，但在30hz闪烁ERG中仍可记录。在荧光素血管造影中，3例患者均显示沿血管拱廊的脉络膜视网膜萎缩特别明显，表明沿血管拱廊的区域是最易发生变性的部分。然而，由于其他2例表现出类似荧光素血管造影结果的患者没有抑制素基因突变，因此这一发现并不是抑制素突变的特异性，而是认为这一变性区域与杆状光感受器的最高分布相对应。然而，本研究首次发现抑制蛋白基因突变与一种常染色体隐性视网膜色素变性有关。

In order to investigate whether a mutation in the arrestin gene causes not only Oguchi disease which is one form of congenital stationary night blindness but also retinitis pigmentosa which is progressive retinal degeneration, we continued mutation screening for arrestin gene and further analyzed the relationship between genotype and phenotype. As a result, we found the same mutation in the arrestin gene (ll47delA) in 3 patients with autosomal recessive retinitis pigmentosa as had been found in patients with Oguchi disease. Of 3 patients, 2 patients showed typical pigmentary retinal degeneration in their fundi and another patient showed central retinitis pigmentosa associated with golden-yellow fundus reflex in the periphery. In electroretinograms, all 3 patients showed decreased a- and b-waves but not completely diminished in standard ERG and also they commonly showed decreased waves but still recordable responses in 30-Hz flicker ERG.In fluorescein angiograms, all 3 patients showed chorioretinal atrophy particularly remarkable along the vascular arcade, indicating that the area along the vascular arcade is the most susceptible portion of degeneration. However, because other 2 patients who showed similar fluorescein angiographic findings had no mutation in the arrestin gene, this finding is not specific for the mutation in the arrestin but rather it is considered that this area of degeneration is corresponded to the highest distribution of rod photoreceptors. Nevertheless, the present study showed that a mutation in the arrestin gene is related to one form of autosomal recessive retinitis pigmentosa for the first time.