Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness
Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness
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DOI：
10.1038/ng0297-175
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发表时间：
1997-02-01
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, S;Sippel, KC;Dryja, TP
Oguchi病是一种由于视杆细胞感光机制故障而引起的静止性夜盲症的复发性遗传形式。患有这种疾病的患者表现出独特的金棕色眼底颜色，这是由于视网膜适应光线而发生的，称为Mizuo现象。最近，在一些日本患者中发现了抑制蛋白（视杆细胞光转导通路的一个成员）的缺陷导致这种疾病（1）。由于视紫红质激酶在被光光子激活后与抑制蛋白一起关闭视紫红质，因此有理由认为某些Oguchi病病例可能是由视紫红质激酶缺陷引起的。本报告描述了一个分析的arrestin和视紫红质激酶基因在三个无关的情况下，Oguchi病。没有检测到arrestin的缺陷，但所有三个病例都有视紫红质激酶基因突变。两例被发现是纯合子的缺失，包括外显子5，预测会导致一个无功能的蛋白质。第三种情况是一个复合杂合子与两个等位基因突变，错义突变（Val 380 Asp）影响的催化结构域中的残基，和移码突变（Ser 536（4-bp del））导致的羧基末端的截断。我们的研究结果表明，视紫红质激酶基因的无效突变是引起Oguchi病的原因之一，并扩展了先天性静止性夜盲症的遗传异质性。
Oguchi disease is a recessively inherited form of stationary night blindness due to malfunction of the rod photoreceptor mechanism. Patients with this disease show a distinctive golden-brown colour of the fundus that occurs as the retina adapts to light, called the Mizuo phenomenon. Recently a defect in arrestin, a member of the rod phototransduction pathway, was found to cause this disease in some Japanese patients(1). As rhodopsin kinase works with arrestin in shutting off rhodopsin after it has been activated by a photon of light, it is reasonable to propose that some cases of Oguchi disease might be caused by defects in rhodopsin kinase. This report describes an analysis of the arrestin and rhodopsin kinase genes in three unrelated cases of Oguchi disease. No defects in arrestin were detected, but all three cases had mutations in the rhodopsin kinase gene. Two cases were found to be homozygous for a deletion encompassing exon 5, predicted to lead to a nonfunctional protein. The third case was a compound heterozygote with two allelic mutations, a missense mutation (Val380Asp) affecting a residue in the catalytic domain, and a frameshift mutation (Ser536(4-bp del)) resulting in truncation of the carboxy terminus. Our results indicate that null mutations in the rhodopsin kinase gene are a cause of Oguchi disease and extend the known genetic heterogeneity in congenital stationary night blindness.