Mutations in RHO are the most common cause of autosomal dominant retinitis pigmentosa. However, the pathogenicity of many RHO variants is questionable. This study was designed to investigate the genotype–phenotype correlation for RHO variants. These RHO variants were collected from the in-house exome sequencing data of 7092 probands suffering from different types of eye conditions. The variants were classified using bioinformatics tools, family segregation, and clinical phenotypes. The RHO variants were assessed using multiple online tools and a genotype–phenotype analysis based on the data collected from of ours, gnomAD, and published literature. Totally, 52 heterozygous variants of RHO were detected in the 7092 probands. Of these 52, 17 were potentially pathogenic, were present in 35 families, and comprised 15 missense variants, one inframe deletion and one nonsense variant. All the 15 missense variants were predicted to be damaging by five different online tools. The analysis of the clinical data of the patients from the 35 families revealed certain common features, of an early damage to both the rods and the cones, relatively preserved visual acuity in adulthood, and mid-peripheral tapetoretinal degeneration with pigmentation or RPE atrophy. Our data, the data from gnomAD, and the systematic review of the 246 previously reported variants suggest that approximately two-thirds of the rare missense variants and most of the truncated variants involving upstream of K296 are likely benign. This study provides a brief summary of the characteristics of the pathogenic RHO variants. It emphasizes that the systematic evaluation of these variants at the individual-gene level is crucial in the current era of clinical genetic testing even for a well-known gene such as RHO.

RHO中的突变是常染色体显性遗传性色素性视网膜炎的最常见原因。然而，许多RHO变体的致病性令人怀疑。本研究旨在研究RHO变异体的基因型与表型的相关性。这些RHO变体是从7092名患有不同类型眼疾的先证者的内部外显子组测序数据中收集的。使用生物信息学工具，家庭隔离和临床表型对变异进行分类。该RHO变种采用多种在线工具和基于与我们，gnomAD收集到的数据的基因型-表型分析，并公开发表的文献进行评估。共有52个RHO杂合变体在7092个先证者中被检测到。在这52个中，有17个具有潜在的致病性，存在于35个科中，包括15个错义变体，1个读框缺失和1个无义变体。预计所有15种错义变体都会受到5种不同的在线工具的破坏。对来自35个家庭的患者的临床数据进行分析后发现，它们具有某些共同特征，即杆和视锥骨早期受损，成年期相对保留的视敏度以及中枢性色素性色素沉着或RPE萎缩引起的周围性圆锥角膜变性。我们的数据，来自gnomAD的数据以及对246个先前报道的变体的系统评价表明，大约三分之二的罕见错义变体和涉及K296上游的大部分截短变体可能是良性的。RHO变体。它强调指出，在当今的临床基因测试时代，即使对于众所周知的基因（如RHO），在个体基因水平上对这些变体进行系统评估也至关重要。