Wong Wendy M, Robson Anthony G, Baker Rebecca A, Arno Gavin, Van Aerschot Joseph, Lin Siying, Moosajee Mariya, Michaelides Michel, Mahroo Omar A, Webster Andrew R
Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.
Centre for Innovation and Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Invest Ophthalmol Vis Sci. 2025 Jul 1;66(9):3. doi: 10.1167/iovs.66.9.3.
To comprehensively characterize the clinical consequences of the CRB1 variant p.(Pro836Thr). In African populations, this variant has an allele frequency of 0.329% (gnomAD v4.1.0).
This study was a retrospective case series of 14 patients from 11 families with molecularly confirmed CRB1-associated retinal dystrophy, each possessing at least one p.(Pro836Thr) variant. The age at onset of visual symptoms, best-corrected visual acuity, imaging findings, and quantitative electrophysiologic measurements of retinal function were analyzed.
The p.(Pro836Thr) variant was homozygous in four families and compound heterozygous in seven families. The familial origins included Nigeria (n = 4), Ghana (n = 3), the Caribbean region (n = 2), and Uganda (n = 1). The median follow-up was 7 years (interquartile range, 3-16). Symptom onset was most common in childhood (eight patients, 57.1%). Reduced central vision was the most frequent presenting symptom (12 patients, 85%). Widefield multimodal imaging revealed peripheral retinal changes in addition to macular changes in three patients. Nine patients had international standard electrophysiology and showed generalized retinal dysfunction with a similar degree of rod and cone system involvement (n = 7) or a clear rod-cone pattern of dysfunction (n = 2). All had pattern electroretinography (ERG) evidence of macular dysfunction.
The study highlights the association of the p.(Pro836Thr) variant with African ancestry and characterizes their key clinical and electrophysiological features. Our study suggests that the p.(Pro836Thr) variant confers a less severe consequence on retinal function and structure than the majority of other reported CRB1 variants. Although retinal imaging may show alterations confined to the macular region, electrophysiology in this series indicates generalized cone and rod photoreceptor dysfunction.
全面描述CRB1基因变体p.(Pro836Thr)的临床后果。在非洲人群中，该变体的等位基因频率为0.329%（gnomAD v4.1.0）。
本研究是一项回顾性病例系列研究，纳入了11个家庭的14例患者，这些患者经分子确诊患有CRB1相关视网膜营养不良，每个患者至少携带一个p.(Pro836Thr)变体。分析了视觉症状的发病年龄、最佳矫正视力、影像学表现以及视网膜功能的定量电生理测量结果。
p.(Pro836Thr)变体在4个家庭中为纯合子，在7个家庭中为复合杂合子。家族起源包括尼日利亚（n = 4）、加纳（n = 3）、加勒比地区（n = 2）和乌干达（n = 1）。中位随访时间为7年（四分位间距，3 - 16年）。症状最常在儿童期出现（8例患者，占比57.1%）。中心视力下降是最常见的首发症状（12例患者，占比85%）。宽视野多模态成像显示，除3例患者有黄斑改变外，还存在周边视网膜改变。9例患者进行了国际标准电生理检查，结果显示存在广泛性视网膜功能障碍，视杆和视锥系统受累程度相似（n = 7）或呈现明显的视杆 - 视锥功能障碍模式（n = 2）。所有患者的图形视网膜电图（ERG）均显示有黄斑功能障碍。
本研究强调了p.(Pro836Thr)变体与非洲血统的关联，并描述了其关键的临床和电生理特征。我们的研究表明，与其他大多数已报道的CRB1变体相比，p.(Pro836Thr)变体对视网膜功能和结构的影响较轻。尽管视网膜成像可能显示仅局限于黄斑区域的改变，但本系列研究中的电生理检查表明存在广泛性的视锥和视杆光感受器功能障碍。
