Audo Isabelle, Friedrich Anne, Mohand-Saïd Saddek, Lancelot Marie-Elise, Antonio Aline, Moskova-Doumanova Veselina, Poch Olivier, Bhattacharya Shomi, Sahel José-Alain, Zeitz Christina
Institut National de la Santé et de la Recherche Médicale, Paris, France.
Arch Ophthalmol. 2010 Aug;128(8):1036-45. doi: 10.1001/archophthalmol.2010.162.
To report a new genetic variant in the rhodopsin gene (RHO) associated with an unusual autosomal dominant retinal phenotype.
Detailed phenotypic characterization was performed on affected family members spanning 4 generations, including family history, best-corrected visual acuity, fundus examination, kinetic and static perimetry, full-field and multifocal electroretinography, fundus autofluorescence, and optical coherence tomography. For genetic testing, coding exons and flanking intronic regions of RHO were amplified with the use of polymerase chain reaction, purified, and sequenced. Cosegregation and control analysis were performed by direct sequencing of exon 3. Subsequent in silico analysis of the mutational consequence on protein function was undertaken.
The onset of symptoms appeared in the fourth decade of life in this family, with moderate night blindness and asymmetrical visual loss. Affected members showed patchy areas of chorioretinal atrophy with decreased electroretinographic response amplitudes for both scotopic and photopic responses but no implicit time shift, consistent with restricted disease. A novel mutation in exon 3 of RHO was identified and represents a c.620T>A transition leading to a p.Met207Lys substitution. It cosegregated with this phenotype and was not identified in a control population.
We report the phenotype-genotype correlation of an unusual autosomal dominant, late-onset restricted chorioretinal degeneration cosegregating with a novel RHO mutation, p.Met207Lys. A p.Met207Arg substitution has previously been reported to cause a distinct, generalized early-onset rod-cone dystrophy. Clinical Relevance These data outline the phenotypic variability associated with RHO mutations. Depending on the localization and the amino acid substitution, patients may show congenital stationary night blindness, rod-cone dystrophy, sector retinitis pigmentosa, or localized chorioretinal atrophy.
报告视紫红质基因（RHO）中一种与不寻常的常染色体显性视网膜表型相关的新基因变异。
对4代受影响家庭成员进行详细的表型特征分析，包括家族史、最佳矫正视力、眼底检查、动态和静态视野检查、全视野和多焦视网膜电图、眼底自发荧光以及光学相干断层扫描。对于基因检测，使用聚合酶链反应扩增RHO的编码外显子和侧翼内含子区域，纯化后进行测序。通过对第3外显子的直接测序进行共分离和对照分析。随后对突变对蛋白质功能的影响进行了计算机模拟分析。
该家族症状出现在生命的第四个十年，有中度夜盲和不对称视力丧失。受影响成员显示脉络膜视网膜萎缩的斑片状区域，暗视和明视反应的视网膜电图反应幅度均降低，但无隐含时间偏移，符合局限性疾病。在RHO的第3外显子中鉴定出一个新突变，代表c.620T>A转换，导致p.Met207Lys替代。它与这种表型共分离，在对照人群中未被发现。
我们报告了一种不寻常的常染色体显性、迟发性局限性脉络膜视网膜变性与一种新的RHO突变p.Met207Lys共分离的表型-基因型相关性。先前已报道p.Met207Arg替代会导致一种独特的、全身性早发性视杆-视锥营养不良。临床相关性这些数据概述了与RHO突变相关的表型变异性。根据定位和氨基酸替代情况，患者可能表现为先天性静止性夜盲、视杆-视锥营养不良、扇形视网膜色素变性或局限性脉络膜视网膜萎缩。
