A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease with markedly reduced cone responses
A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease with markedly reduced cone responses
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DOI：
10.1016/j.ophtha.2006.05.069
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发表时间：
2007-01-01
期刊：
影响因子：
13.7
通讯作者：
Kitahara, Kenji
中科院分区：
文献类型：
--
作者：
Hayashi, Takaaki;Gekka, Tamaki;Kitahara, Kenji
目的：到目前为止，日本报道的Oguchi病患者中唯一报道的突变是SAG(Arrestin)基因。Oguchi病是一种罕见的常染色体隐性遗传静止性夜盲。本研究的目的是描述2例日本Oguchi病患者的眼部特征和一种新的GRK1基因突变。设计：分子遗传学和观察性病例研究。参与者：包括2个Oguchi病兄弟姐妹(1名35岁男性和1名31岁女性)的近亲家庭。方法：评估最佳矫正视力(BCVA)、眼底检查、Goldmann视野检查、色觉测试和全场视网膜电图(ERGs)。用聚合酶链式反应扩增和直接测序的方法对SAG和GRK1基因进行突变筛查。主要观察指标：GRK1基因突变、BCVA、色觉、眼底照片、视野和ERG检查。结果：分子分析发现两例患者GRK1基因均存在一种新的纯合错义突变(p.P391H)。Pro 391不仅位于重要的催化结构域，而且是GRK1同源物和同源物中的一个系统发育保守的氨基酸残基。未发现SAG基因突变。未受影响的父母是突变的杂合子携带者。两例患者均为夜盲，双眼视力为1.5BCVA，色觉正常，眼底表现典型的金黄色变色。男性同胞的视野正常。两名患者的ERG均未显示杆状B波，标准组合反应降低，单次闪光锥体反应和30赫兹闪烁反应显著降低。结论：在2例日本大口病同胞中发现了一种新的纯合子GRK1突变(p.P391H)。这2名患者的视功能没有随着年龄的增长而恶化，表明疾病是稳定的。这是第一例与GRK11相关的Oguchi病患者的锥体反应显著降低的报告。
Purpose: The only mutations reported to date in Japanese patients with Oguchi disease, a rare form of stationary night blindness with autosomal recessive transmission, have been in the SAG (arrestin) gene. The objective of this study was to describe the ophthalmic features and a novel mutation in the GRK1 (rhodopsin kinase) gene in 2 Japanese patients with Oguchi disease.Design: Molecular genetic and observational case study.Participants: A consanguineous family including 2 siblings with Oguchi disease (a 35-year-old man and a 31-year-old woman).Methods: Best-corrected visual acuity (BCVA), fundus examinations, Goldmann perimetry, color vision tests, and full-field electroretinograms (ERGs) were evaluated. Mutation screening of the SAG and GRK1 genes was performed with polymerase chain reaction amplification and direct sequencing. Main Outcome Measures: Mutations in the GRK1 gene, BCVA, color vision, fundus photographs, visual fields, and ERG findings.Results: Molecular analysis revealed a novel homozygous missense mutation (p.P391 H) in the GRK1 gene in both patients. Proline 391 is not only within the functionally important catalytic domain, but is also a phylogenetically conserved amino acid residue among GRK1 orthologs and homologs. No mutation was found in the SAG gene. The unaffected parents were heterozygous carriers of the mutation. Both patients had night blindness, 1.5 BCVA for each eye, normal color vision, and typical fundus appearance with golden-yellow discoloration. The visual fields were normal in the male sibling. The ERGs showed no rod B waves, reduced standard combined responses, and markedly reduced single-flash cone and 30-Hz flicker responses in both patients.Conclusions: A novel homozygous GRK1 mutation (p.P391H) was found in 2 Japanese siblings with Oguchi disease. Visual function in the 2 patients has not deteriorated with age, indicating that the disease is stationary. This is the first report of any patient with GRK11-associated Oguchi disease with markedly reduced cone responses.