Choi Seung Woo, Woo Se Joon, Kim Minji, Lee Sejoon, Joo Kwangsic
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.
Transl Vis Sci Technol. 2024 Aug 1;13(8):2. doi: 10.1167/tvst.13.8.2.
Homozygous hypomorphic variants of the RP1 gene, including c.5797C>T, p.Arg1933Ter, have traditionally been considered non-pathogenic. This study aimed to elucidate the clinical manifestations of late-onset, slowly progressive cone/macular dystrophy in patients homozygous for p.Arg1933Ter in the RP1 gene.
Five patients with biallelic p.Arg1933Ter in RP1 were retrospectively recruited, and their clinical profiles were analyzed. Copy number variation analysis and Alu insertion assessment of genes associated with inherited retinal diseases were conducted. The results of comprehensive ophthalmological examinations, multimodal imaging, and full-field electroretinogram tests were analyzed.
No specific sequencing errors or structural variations associated with the clinical phenotypes were identified. Alu element insertion in RP1 was not detected. The mean ± SD age at the first visit was 62.2 ± 9.8 years, with symptoms typically starting between 45 and 50 years of age. Two patients exhibited a mild form of cone/macular dystrophy, characterized by a relatively preserved fundus appearance and blurring of the ellipsoid zone on optical coherence tomography. Three patients had late-onset cone/macular dystrophy with significant atrophy.
To our knowledge, this study is the first to report that a homozygous hypomorphic variant of RP1, previously considered non-pathogenic, leads to cone/macular dystrophy.
The study introduces novel possibilities suggesting that the homozygous hypomorphic variant of RP1 may be linked to variant pathogenicity.
传统上认为RP1基因的纯合子低表达变异，包括c.5797C>T、p.Arg1933Ter，是非致病性的。本研究旨在阐明RP1基因p.Arg1933Ter纯合子患者迟发性、缓慢进展性视锥/黄斑营养不良的临床表现。
回顾性招募了5例RP1基因双等位基因p.Arg1933Ter的患者，并分析了他们的临床资料。对与遗传性视网膜疾病相关的基因进行了拷贝数变异分析和Alu插入评估。分析了综合眼科检查、多模态成像和全视野视网膜电图检查的结果。
未发现与临床表型相关的特定测序错误或结构变异。未检测到RP1中的Alu元件插入。首次就诊时的平均年龄±标准差为62.2±9.8岁，症状通常始于45至50岁之间。两名患者表现为轻度视锥/黄斑营养不良，其特征是眼底外观相对保留，光学相干断层扫描显示椭圆体带模糊。三名患者患有迟发性视锥/黄斑营养不良并伴有明显萎缩。
据我们所知，本研究首次报道了RP1基因的纯合子低表达变异，此前被认为是非致病性的，可导致视锥/黄斑营养不良。
该研究提出了新的可能性，表明RP1基因的纯合子低表达变异可能与变异致病性有关。
