Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus
Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus
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DOI：
10.1038/9707
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发表时间：
1999-06-01
期刊：
影响因子：
30.8
通讯作者：
Dryja, TP
中科院分区：
文献类型：
--
作者：
Yamamoto, H;Simon, A;Dryja, TP
产生II-顺式视黄醇的代谢途径对视力很重要，因为这种类视黄醇是存在于视紫红质和色调视蛋白中的发色团。视锥细胞和视杆细胞色素吸收光的光子后产生的全反式视黄醛通过视网膜的视网膜色素上皮细胞和Muller细胞再循环回到11-顺式视黄醛。涉及的几种酶：最近被纯化和分子克隆（1-3）：在这里，我们专注于II-顺式视黄醇脱氢酶（由基因RDH 5编码;染色体12 q1 - 3 -14;参考文献4），这是该途径中的第一个克隆酶。这种微粒体酶在视网膜色素上皮中含量丰富（5），已提出在视网膜色素上皮中催化II-顺式视黄醇转化为II-顺式视黄醇。我们评估了以视网膜下斑点为特征的遗传性视网膜疾病患者（白斑视网膜炎和白斑眼底）和典型显性或隐性视网膜色素变性患者的RDH 5突变。仅在两名不相关的患者中发现了突变，这两名患者均患有眼底白斑;他们在各自的家族中与疾病分离。与野生型序列的重组酶相比，重组突变体II-顺式视黄醇脱氢酶的活性降低。我们的研究结果表明，在RDH 5突变等位基因是眼底albipunctatus，一种罕见的形式，固定夜盲症的特点是延迟再生的锥和杆色素的原因。
The:metabolic pathways that produce Il-cis retinal are important for vision because this retinoid is the chromophore residing in rhodopsin and the tone opsins. The all-trans retinal that is generated after cone and rod photopigments absorb photons of light is recycled back to 11-cis retinal by the retinal pigment epithelium and Muller cells: of the retina. Several of the enzymes involved have:recently been purified and molecularly cloned (1-3);:here we focus on Il-cis retinol dehydrogenase (encoded by the gene RDH5; chromosome 12q13-14; ref. 4), the first cloned enzyme in this pathway. This microsomal enzyme is abundant in the retinal pigment epithelium(5), where it has been proposed to catalyse the conversion of Il-cis retinol to Il-cis retinal. We evaluated patients with hereditary retinal diseases featuring subretinal spots (retinitis punctata albescens and fundus albipunctatus) and patients with typical dominant or recessive retinitis pigmentosa for mutations in RDH5. Mutations were found only in two unrelated patients, both with fundus albipunctatus; they segregated with disease in the respective families. Recombinant mutant Il-cis retinol dehydrogenases had reduced activity compared with recombinant enzyme with wild-type sequence. Our results suggest that mutant alleles in RDH5 are a cause of fundus albipunctatus, a rare form of stationary night blindness characterized by a delay in the regeneration of cone and rod photopigments.