Hayashi Takaaki, Gekka Tamaki, Takeuchi Tomokazu, Goto-Omoto Satoshi, Kitahara Kenji
Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan.
Ophthalmology. 2007 Jan;114(1):134-41. doi: 10.1016/j.ophtha.2006.05.069. Epub 2006 Oct 27.
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.
Molecular genetic and observational case study.
A consanguineous family including 2 siblings with Oguchi disease (a 35-year-old man and a 31-year-old woman).
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.
Mutations in the GRK1 gene, BCVA, color vision, fundus photographs, visual fields, and ERG findings.
Molecular analysis revealed a novel homozygous missense mutation (p.P391H) 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.
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 GRK1-associated Oguchi disease with markedly reduced cone responses.
小口病是一种罕见的常染色体隐性遗传性静止性夜盲症，迄今为止，日本小口病患者中报告的唯一突变存在于SAG（抑制蛋白）基因中。本研究的目的是描述2例日本小口病患者的眼科特征以及GRK1（视紫红质激酶）基因中的一种新突变。
分子遗传学和观察性病例研究。
一个近亲家庭，包括2名患有小口病的兄弟姐妹（一名35岁男性和一名31岁女性）。
评估最佳矫正视力（BCVA）、眼底检查、Goldmann视野检查、色觉测试和全视野视网膜电图（ERG）。采用聚合酶链反应扩增和直接测序对SAG和GRK1基因进行突变筛查。
GRK1基因中的突变、BCVA、色觉、眼底照片、视野和ERG结果。
分子分析显示，两名患者的GRK1基因均存在一种新的纯合错义突变（p.P391H）。脯氨酸391不仅位于功能重要的催化结构域内，而且是GRK1直系同源物和同源物之间在系统发育上保守的氨基酸残基。在SAG基因中未发现突变。未受影响的父母是该突变的杂合携带者。两名患者均有夜盲症，每只眼睛的BCVA为1.5，色觉正常，眼底外观典型，呈金黄色变色。男性兄弟姐妹的视野正常。两名患者的ERG均显示无视杆B波、标准联合反应降低，单闪光视锥和30Hz闪烁反应明显降低。
在2名患有小口病的日本兄弟姐妹中发现了一种新的纯合GRK1突变（p.P391H）。这两名患者的视觉功能并未随年龄增长而恶化，表明该疾病是静止性的。这是首例GRK1相关小口病患者视锥反应明显降低的报告。
