ABSTRACT

Background

Mutations in the splicing factor pre-messenger RNA processing factor 31 (PRPF31) gene cause autosomal dominant retinitis pigmentosa 11 (RP11) through a haplo-insufficiency mechanism. We describe the phenotype and progression of microperimetry and autofluorescence endpoints in an Indigenous Australian RP11 family.

Patients and Methods

Ophthalmic examination, optical coherence tomography, fundus autofluorescence and microperimetry were performed at baseline and every 6–12 months. Baseline and annual change in best-corrected visual acuity (BCVA), microperimetry mean sensitivity (MS) and number of scotoma loci, residual ellipsoid zone (EZ) span and hyperautofluorescent ring (HAR) area were reported. Next-generation and Sanger sequencing were performed in available members.

Results

12 affected members from three generations were examined. Mean (SD, range) age at onset of symptoms was 11 (4.5, 4–19) years. MS declined steadily from the third decade and EZ span and HAR area declined rapidly during the second decade. Serial microperimetry showed negligible change in MS over 2–3 years. However, mean EZ span, near-infrared and short-wavelength HAR area reduction was 203 (6.4%) µm/year, 1.8 (8.7%) mm²/year and 1.1 (8.6%) mm²/year, respectively. Genetic testing was performed on 11 affected and 10 asymptomatic members and PRPF31 c.1205 C > A (p.Ser402Ter) mutation was detected in all affected and two asymptomatic members (non-penetrant carriers).

Conclusions

Our findings suggest that in the studied cohort, the optimal window for therapeutic intervention is the second decade of life and residual EZ span and HAR area can be considered as efficacy outcome measures. Further studies on larger samples with different PRPF31 mutations and longer follow-up duration are recommended.

中文翻译：

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探索微视野和自发荧光终点监测 PRPF31 相关视网膜病变的疾病进展。

摘要

背景

剪接因子前信使 RNA 加工因子 31 ( PRPF31 ) 基因的突变通过单倍体不足机制导致常染色体显性色素性视网膜炎 11 (RP11)。我们描述了澳大利亚土著 RP11 家族中微视野和自发荧光终点的表型和进展。

患者和方法

在基线和每 6-12 个月进行眼科检查、光学相干断层扫描、眼底自发荧光和显微视野检查。报告了最佳矫正视力 (BCVA)、微视野平均灵敏度 (MS) 和暗点位点数、残留椭球区 (EZ) 跨度和超自发荧光环 (HAR) 区域的基线和年度变化。在现有成员中进行了下一代和 Sanger 测序。

结果

对来自三代人的 12 名受影响成员进行了检查。出现症状的平均（SD，范围）年龄为 11 (4.5, 4-19) 岁。MS 从第三个十年开始稳步下降，EZ 跨度和 HAR 区域在第二个十年迅速下降。连续微视野测量显示 MS 在 2-3 年内的变化可以忽略不计。然而，平均 EZ 跨度、近红外和短波长 HAR 面积减少分别为 203 (6.4%) µm/年、1.8 (8.7%) mm ² /年和 1.1 (8.6%) mm ² /年。对 11 名受影响成员和 10 名无症状成员进行了基因检测，并在所有受影响成员和两名无症状成员（非渗透携带者）中检测到PRPF31 c.1205 C > A (p.Ser402Ter) 突变。

结论

我们的研究结果表明，在所研究的队列中，治疗干预的最佳窗口是生命的第二个十年，残余 EZ 跨度和 HAR 面积可被视为疗效结果指标。建议对具有不同PRPF31 突变和更长随访时间的更大样本进行进一步研究。