Jung Young Hoon, Kwak Jay Jiyong, Joo Kwangsic, Lee Hyuk Jun, Park Kyu Hyung, Kim Min Seok, Lee Eun Kyoung, Byeon Suk Ho, Lee Christopher Seungkyu, Han Jinu, Lee Junwon, Yoon Chang Ki, Woo Se Joon
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Institute of Vision Research, Department of Ophthalmology, Severance Eye Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Front Genet. 2023 Aug 29;14:1240067. doi: 10.3389/fgene.2023.1240067. eCollection 2023.
To investigate the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (-associated RP). We conducted a retrospective, multicenter, observational cohort study. We reviewed the medical records of 42 patients with -associated RP of 36 families who visited 4 hospitals in Korea. Patients with molecular confirmation of pathogenic variants of the gene were included. The patients were divided into two subgroups: the generalized and sector RP groups. A central visual field of the better-seeing eye of <10° or a best-corrected visual acuity of the better-seeing eye <20/40 indicated the progression to late-stage RP. The mean age at which symptoms first appeared was 26.3 ± 17.9 years (range: 8-78 years), and the mean follow-up period was 80.9 ± 68.7 months (range: 6-268 months). At the last follow-up visit, the generalized RP group showed a significantly higher rate of visual field impairment progression to late-stage RP than that of the sector RP group (22 of 35 [62.9%] vs. 0 of 7 [0.0%], = 0.003). No cases in the sector RP group progressed to generalized RP. Best-corrected visual acuity deterioration to late-stage RP was observed only in the generalized RP group (13 of 35 patients; 37.1%), whereas no deterioration was observed in the sector RP group. We identified 16 known and three novel mutations, including two missense mutations (p.T108P and p.G121R) and one deletion mutation (p.P347_A348del). The pathogenic variants were most frequently detected in exon 1 (14 of 36 [38.9%]). The most common pathogenic variants were p.P347L and T17M (5 of 36 [13.9%] families). Among 42 patients of 36 families, 35 patients of 29 families (80.6%) presented with the generalized RP phenotype, and seven patients of seven families (19.4%) presented with the sector RP phenotype. Three variants (p.T17M, p.G101E, and p.E181K) presented with both the generalized and sector RP phenotypes. This multicenter cohort study provided information on the clinical and genetic features of -associated RP in Koreans. It is clinically important to expand the genetic spectrum and understand genotype-phenotype correlations to ultimately facilitate the development of gene therapy.
为了研究患有视紫红质相关性视网膜色素变性(-相关性RP)的韩国人的临床特征、自然病程和遗传特征。我们进行了一项回顾性、多中心、观察性队列研究。我们回顾了在韩国4家医院就诊的36个家庭的42例-相关性RP患者的病历。纳入分子确诊有该基因致病变异的患者。患者被分为两个亚组:弥漫性和扇形RP组。较好眼的中心视野<10°或较好眼的最佳矫正视力<20/40表明进展至晚期RP。症状首次出现的平均年龄为26.3±17.9岁(范围:8 - 78岁),平均随访期为80.9±68.7个月(范围:6 - 268个月)。在最后一次随访时,弥漫性RP组进展至晚期RP的视野损害发生率显著高于扇形RP组(35例中的22例[62.9%]对7例中的0例[0.0%],P = 0.003)。扇形RP组中无病例进展为弥漫性RP。仅在弥漫性RP组中观察到最佳矫正视力恶化至晚期RP(35例患者中的13例;37.1%),而扇形RP组中未观察到恶化。我们鉴定出16个已知和3个新的该基因突变,包括2个错义突变(p.T108P和p.G121R)和1个缺失突变(p.P347_A348del)。致病变异最常在外显子1中检测到(36例中的14例[38.9%])。最常见的致病变异是p.P347L和T17M(36例中的5例[13.9%]家庭)。在36个家庭的42例患者中,29个家庭的35例患者(80.6%)表现为弥漫性RP表型,7个家庭的7例患者(19.4%)表现为扇形RP表型。3个变异(p.T17M、p.G101E和p.E181K)同时表现出弥漫性和扇形RP表型。这项多中心队列研究提供了韩国人-相关性RP的临床和遗传特征信息。扩展遗传谱并理解基因型 - 表型相关性对于最终促进基因治疗的发展具有重要临床意义。