Abstract：
To describe the clinical phenotype of retinitis pigmentosa (RP) caused by PRPF31-variants and clinical characterization of asymptomatic PRPF31 carriers.
We conducted a descriptive cross-sectional deep phenotyping study. We included subjects with PRPF31 variants predicted to be disease-causing, both individuals with RP and asymptomatic carriers. Participants underwent a comprehensive clinical examination of standard visual function parameters (visual acuity, contrast sensitivity, Goldmann visual field), full-field stimulus threshold (FST), full-field electroretinogram (ff-ERG), and a structural investigation with slit lamp and multimodal imaging. We used Spearman correlation analyses to evaluate associations between quantitative outcomes.
We included 21 individuals with disease-causing PRPF31-variants: 16 symptomatic and 5 asymptomatic subjects. The symptomatic subjects demonstrated a typical RP phenotype with constricted visual fields, extinguished ff-ERG, and disrupted outer retinal anatomy. FST was impaired and correlated significantly with other outcome measures in RP subjects. Structure-function correlations with Spearman correlation analysis showed moderate correlation coefficients due to a few outliers in each analysis. The asymptomatic individuals had normal best-corrected visual acuity and visual fields, but showed reduced ff-ERG amplitudes, borderline FST sensitivity, and structural abnormalities on OCT and fundoscopy.
RP11 has a typical RP phenotype but varies in terms of severity. FST measurements correlated well with other functional and structural metrics and may be a reliable outcome measure in future trials as it is sensitive to a broad range of disease severities. Asymptomatic carriers showed sub-clinical disease manifestations, and our findings underline that reported non-penetrance in PRPF31-related RP is not an all-or-none phenomenon.
We conducted a descriptive cross-sectional deep phenotyping study. We included subjects with PRPF31 variants predicted to be disease-causing, both individuals with RP and asymptomatic carriers. Participants underwent a comprehensive clinical examination of standard visual function parameters (visual acuity, contrast sensitivity, Goldmann visual field), full-field stimulus threshold (FST), full-field electroretinogram (ff-ERG), and a structural investigation with slit lamp and multimodal imaging. We used Spearman correlation analyses to evaluate associations between quantitative outcomes.
We included 21 individuals with disease-causing PRPF31-variants: 16 symptomatic and 5 asymptomatic subjects. The symptomatic subjects demonstrated a typical RP phenotype with constricted visual fields, extinguished ff-ERG, and disrupted outer retinal anatomy. FST was impaired and correlated significantly with other outcome measures in RP subjects. Structure-function correlations with Spearman correlation analysis showed moderate correlation coefficients due to a few outliers in each analysis. The asymptomatic individuals had normal best-corrected visual acuity and visual fields, but showed reduced ff-ERG amplitudes, borderline FST sensitivity, and structural abnormalities on OCT and fundoscopy.
RP11 has a typical RP phenotype but varies in terms of severity. FST measurements correlated well with other functional and structural metrics and may be a reliable outcome measure in future trials as it is sensitive to a broad range of disease severities. Asymptomatic carriers showed sub-clinical disease manifestations, and our findings underline that reported non-penetrance in PRPF31-related RP is not an all-or-none phenomenon.
摘要：
■描述由PRPF31变体引起的色素性视网膜炎（RP）的临床表型和无症状PRPF31携带者的临床特征。
■我们进行了描述性的横断面深层表型研究。我们纳入了预测为致病的PRPF31变体的受试者，患有RP和无症状携带者。参与者接受了标准视觉功能参数的全面临床检查（视敏度，对比敏感度,戈德曼视野)，全场刺激阈值（FST），全场视网膜电图（ff-ERG），以及裂隙灯和多模态成像的结构研究。我们使用Spearman相关性分析来评估定量结果之间的关联。
■我们包括21名具有致病PRPF31变异体的个体：16名有症状受试者和5名无症状受试者。有症状的受试者表现出典型的RP表型，视野狭窄，熄灭的ff-ERG，破坏了外部视网膜解剖结构.RP受试者的FST受损，并与其他结局指标显着相关。Spearman相关分析的结构-功能相关性显示出中等的相关系数，因为每个分析中都有一些异常值。无症状个体具有正常的最佳矫正视力和视野，但显示ff-ERG振幅降低，边界FST灵敏度,OCT和眼底镜检查的结构异常。
■RP11具有典型的RP表型，但严重程度不同。FST测量与其他功能和结构指标相关良好，并且可能是未来试验中可靠的结果指标，因为它对广泛的疾病严重程度敏感。无症状携带者表现为亚临床疾病表现,我们的发现强调，在PRPF31相关RP中报告的非外显率不是全无现象。
■我们进行了描述性的横断面深层表型研究。我们纳入了预测为致病的PRPF31变体的受试者，患有RP和无症状携带者。参与者接受了标准视觉功能参数的全面临床检查（视敏度，对比敏感度,戈德曼视野)，全场刺激阈值（FST），全场视网膜电图（ff-ERG），以及裂隙灯和多模态成像的结构研究。我们使用Spearman相关性分析来评估定量结果之间的关联。
■我们包括21名具有致病PRPF31变异体的个体：16名有症状受试者和5名无症状受试者。有症状的受试者表现出典型的RP表型，视野狭窄，熄灭的ff-ERG，破坏了外部视网膜解剖结构.RP受试者的FST受损，并与其他结局指标显着相关。Spearman相关分析的结构-功能相关性显示出中等的相关系数，因为每个分析中都有一些异常值。无症状个体具有正常的最佳矫正视力和视野，但显示ff-ERG振幅降低，边界FST灵敏度,OCT和眼底镜检查的结构异常。
■RP11具有典型的RP表型，但严重程度不同。FST测量与其他功能和结构指标相关良好，并且可能是未来试验中可靠的结果指标，因为它对广泛的疾病严重程度敏感。无症状携带者表现为亚临床疾病表现,我们的发现强调，在PRPF31相关RP中报告的非外显率不是全无现象。
