Molecular Genetic Analysis of Retinitis Pigmentosa

为了研究arrestin基因突变是否不仅会导致Oguchi病(一种先天性静止性夜盲)，也会导致视网膜色素变性(进行性视网膜变性)，我们继续对arrestin基因进行突变筛查，并进一步分析了基因与表型的关系。结果，我们在3例常染色体隐性遗传性视网膜色素变性患者中发现了与Oguchi病患者相同的arrestin基因(1147delA)突变。3例中，2例表现为典型的眼底色素性视网膜变性，1例表现为中心性视网膜色素变性伴周边金黄色眼底反射。在视网膜电图中，3例患者在标准ERG中均表现为a波和b波降低，但在标准ERG中并未完全消失；在30赫兹闪烁ERG中，3例患者通常表现为波形降低，但仍可记录到反应。在荧光素血管造影中，3例患者均显示沿血管拱部的脉络膜视网膜萎缩尤其明显，表明沿血管拱部的区域是最易发生变性的部位。然而，由于另2例患者的荧光血管造影结果相似，没有arrestin基因突变，这一发现并不是arrestin突变的特异性，而是被认为该变性区域与杆状感光细胞的最高分布相对应。然而，本研究首次表明arrestin基因的突变与一种形式的常染色体隐性遗传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.