Neidhardt John, Barthelmes Daniel, Farahmand Firouzeh, Fleischhauer Johannes C, Berger Wolfgang
University of Zurich, Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, Schwerzenbach, Switzerland.
Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1630-5. doi: 10.1167/iovs.05-1317.
Identification of a novel rhodopsin mutation in a family with retinitis pigmentosa and comparison of the clinical phenotype to a known mutation at the same amino acid position.
Screening for mutations in rhodopsin was performed in 78 patients with retinitis pigmentosa. All exons and flanking intronic regions were amplified by PCR, sequenced, and compared to the reference sequence derived from the National Center for Biotechnology Information (NCBI, Bethesda, MD) database. Patients were characterized clinically according to the results of best corrected visual acuity testing (BCVA), slit lamp examination (SLE), funduscopy, Goldmann perimetry (GP), dark adaptometry (DA), and electroretinography (ERG). Structural analyses of the rhodopsin protein were performed with the Swiss-Pdb Viewer program available on-line (http://www.expasy.org.spdvbv/ provided in the public domain by Swiss Institute of Bioinformatics, Geneva, Switzerland).
A novel rhodopsin mutation (Gly90Val) was identified in a Swiss family of three generations. The pedigree indicated autosomal dominant inheritance. No additional mutation was found in this family in other autosomal dominant genes. The BCVA of affected family members ranged from 20/25 to 20/20. Fundus examination showed fine pigment mottling in patients of the third generation and well-defined bone spicules in patients of the second generation. GP showed concentric constriction. DA demonstrated monophasic cone adaptation only. ERG revealed severely reduced rod and cone signals. The clinical picture is compatible with retinitis pigmentosa. A previously reported amino acid substitution at the same position in rhodopsin leads to a phenotype resembling night blindness in mutation carriers, whereas patients reported in the current study showed the classic retinitis pigmentosa phenotype. The effect of different amino acid substitutions on the three-dimensional structure of rhodopsin was analyzed by homology modeling. Distinct distortions of position 90 (shifts in amino acids 112 and 113) and additional hydrogen bonds were found.
Different amino acid substitutions at position 90 of rhodopsin can lead to night blindness or retinitis pigmentosa. The data suggest that the property of the substituted amino acid distinguishes between the phenotypes.
在一个患有色素性视网膜炎的家族中鉴定一种新的视紫红质突变，并将临床表型与同一氨基酸位置的已知突变进行比较。
对78例色素性视网膜炎患者进行视紫红质突变筛查。通过聚合酶链反应（PCR）扩增所有外显子及其侧翼内含子区域，进行测序，并与来自美国国立生物技术信息中心（NCBI，马里兰州贝塞斯达）数据库的参考序列进行比较。根据最佳矫正视力测试（BCVA）、裂隙灯检查（SLE）、眼底镜检查、戈德曼视野计检查（GP）、暗适应检查（DA）和视网膜电图（ERG）的结果对患者进行临床特征分析。使用在线提供的瑞士蛋白质数据浏览器程序（http://www.expasy.org.spdvbv/，由瑞士生物信息学研究所免费提供，瑞士日内瓦）对视紫红质蛋白进行结构分析。
在一个三代瑞士家族中鉴定出一种新的视紫红质突变（Gly90Val）。家系显示常染色体显性遗传。在该家族的其他常染色体显性基因中未发现其他突变。受影响家族成员的BCVA范围为20/25至20/20。眼底检查显示第三代患者有细小的色素斑点，第二代患者有明确的骨针状改变。GP显示同心圆状收缩。DA仅显示单相锥体适应。ERG显示杆体和锥体信号严重降低。临床症状与色素性视网膜炎相符。先前报道的视紫红质同一位置的氨基酸替代导致突变携带者出现类似夜盲的表型，而本研究报道的患者表现出典型的色素性视网膜炎表型。通过同源建模分析了不同氨基酸替代对视紫红质三维结构的影响。发现90位有明显扭曲（112和113位氨基酸移位）以及额外的氢键。
视紫红质90位不同的氨基酸替代可导致夜盲或色素性视网膜炎。数据表明，替代氨基酸的特性区分了不同的表型。
