Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy.
Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1547-1555. doi: 10.1167/iovs.18-25501.
To evaluate the disease progression in patients with clinical and genetic diagnoses of choroideremia during a long-term follow-up and to investigate the relationship between pathogenic variants in the CHM/REP1 gene and disease phenotypes.
We performed a retrospective longitudinal study on 51 affected men by reviewing medical charts at baseline and follow-up visits to extract the following ocular findings: best-corrected visual acuity, Goldmann visual field, optical coherence tomography, microperimetry. Data obtained from the analysis of DNA and mRNA were reevaluated for genetic classification of patients.
The longitudinal analysis showed a significant (P < 0.001) worsening of best-corrected visual acuity with a mean rate of 0.011 logMar per year before 50 years and 0.025 logMar per year after 50 years. Similarly, V4e Goldmann visual field area significantly (P ≤ 0.01) decreased at a mean rate of 2.7% per year before 40 years and 5.7% after 40 years. Moreover, we observed a significant (P < 0.05) decrease of macular sensitivity with a mean rate of 5.0% per year and a decrease of mean macular thickness with a mean rate of 0.8% per year. We classified our patients into two groups according to the expression of the CHM/REP1 gene transcript and observed that mutations leading to mRNA absence are associated with an earlier best-corrected visual acuity and Goldmann visual field loss.
Our analysis of morphological and functional parameters in choroideremia patients showed a slow disease progression, particularly in the first decades of life. Overall, reevaluation of clinical and molecular data suggests exploring the genotype-phenotype relationship based on CHM/REP1 transcript expression.
在长期随访中评估具有临床和遗传诊断的脉络膜视网膜变性患者的疾病进展，并研究 CHM/REP1 基因突变与疾病表型之间的关系。
我们通过回顾基线和随访就诊的病历，对 51 名受累男性患者进行了回顾性纵向研究，以提取以下眼部发现：最佳矫正视力、Goldmann 视野、光学相干断层扫描、微视野。从 DNA 和 mRNA 分析中获得的数据用于重新评估患者的基因分类。
纵向分析显示，最佳矫正视力显著（P<0.001）恶化，50 岁前平均每年下降 0.011 logMar，50 岁后平均每年下降 0.025 logMar。同样，V4e Goldmann 视野面积也显著（P≤0.01）下降，40 岁前平均每年下降 2.7%，40 岁后下降 5.7%。此外，我们观察到黄斑敏感性显著（P<0.05）下降，平均每年下降 5.0%，黄斑平均厚度平均每年下降 0.8%。我们根据 CHM/REP1 基因转录本的表达将患者分为两组，并观察到导致 mRNA 缺失的突变与较早的最佳矫正视力和 Goldmann 视野丧失相关。
我们对脉络膜视网膜变性患者形态和功能参数的分析表明，疾病进展缓慢，尤其是在生命的头几十年。总体而言，对临床和分子数据的重新评估表明，基于 CHM/REP1 转录本表达探索基因型-表型关系。
