Pathogenic Variants in CEP290 or IQCB1 Cause Earlier-Onset Retinopathy in Senior-Loken Syndrome Compared to Those in INVS, NPHP3, or NPHP4
Pathogenic Variants in CEP290 or IQCB1 Cause Earlier-Onset Retinopathy in Senior-Loken Syndrome Compared to Those in INVS, NPHP3, or NPHP4
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DOI：
10.1016/j.ajo.2023.03.025
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发表时间：
2023-05-15
影响因子：
4.2
通讯作者：
Zhang, Qingjiong
中科院分区：
文献类型：
--
作者：
Wang, Junwen;Li, Shiqiang;Zhang, Qingjiong
中心点 目的：Senior-Loken 综合征 (SLSN) 是一种常染色体隐性遗传疾病，以视网膜病变和肾痨为特征。本研究旨在根据内部数据集和文献综述评估不同表型是否与 10 个 SLSN 相关基因的不同变异或子集相关。中心点设计：回顾性病例系列。中心点方法：SLSN 相关基因双等位基因变异的患者，包括 NPHP1、INVS、NPHP3、NPHP4、IQCB1、CEP290、SDCCAG8、招募了 WDR19、CEP164 和 TRAF3IP1。收集眼表型和肾病病历进行综合分析。中心点结果：70个无亲缘关系家系的74名患者中鉴定出5个基因变异，包括CEP290（61.4%）、IQCB1（28.6%）、NPHP1（4.2%）、NPHP4（2.9%）和WDR19（2.9%）。视网膜病变发病的中位年龄约为 1 个月（自出生起）。眼球震颤是 CEP290（44 例中的 28 例，63.6%）或 IQCB1（22 例中的 19 例，86.4%）变异患者中最常见的初始体征。 55 名患者中有 53 名（96.4%）的视锥细胞和视杆细胞反应消失。在 CEP290 和 IQCB1 相关患者中观察到特征性眼底变化。随访期间，74 名患者中的 70 名被转诊至肾病科，其中 62 名患者 (88.6%) 中位年龄为 6 岁，但 8 名患者 (11.4%) 年龄约为 9 岁，未发现肾结核。 中心点结论：CEP290 或 IQCB1 致病性变异患者早期出现视网膜病变，而其他携带 INVS、NPHP3 或NPHP4 变体首先发展为肾病。因此，了解遗传和临床特征可能有助于 SLSN 的临床管理，特别是对眼睛首先受影响的患者进行肾脏问题的早期干预。 （美国眼科杂志 2023；252：188-204。(c) 2023 Elsevier Inc. 保留所有权利。）
center dot PURPOSE: Senior-Loken syndrome (SLSN) is an auto-somal recessive disorder characterized by retinopathy and nephronophthisis. This study aimed to evaluate whether different phenotypes are associated with different vari-ants or subsets of 10 SLSN-associated genes based on an in-house data set and a literature review.center dot DESIGN: Retrospective case series.center dot METHODS: Patients with biallelic variants in SLSN-associated genes, including NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, SDCCAG8, WDR19, CEP164, and TRAF3IP1, were recruited. Ocular phe-notypes and nephrology medical records were collected for comprehensive analysis.center dot RESULTS: Variants in 5 genes were identified in 74 patients from 70 unrelated families, including CEP290 (61.4%), IQCB1 (28.6%), NPHP1 (4.2%), NPHP4 (2.9%), and WDR19 (2.9%). The median age at the onset of retinopathy was approximately 1 month (since birth). Nystagmus was the most common initial sign in patients with CEP290 (28 of 44, 63.6%) or IQCB1 (19 of 22, 86.4%) variants. Cone and rod responses were extinguished in 53 of 55 patients (96.4%). Char-acteristic fundus changes were observed in CEP290- and IQCB1-associated patients. During follow-up, 70 of the 74 patients were referred to nephrology, among whom nephronophthisis was not detected in 62 patients (88.6%) at a median age of 6 years but presented in 8 patients (11.4%) aged approximately 9 years.center dot CONCLUSIONS: Patients with pathogenic variants in CEP290 or IQCB1 presented early with retinopathy, whereas other patients with INVS, NPHP3, or NPHP4 variants first developed nephropathy. Therefore, aware -ness of the genetic and clinical features may facilitate the clinical management of SLSN, especially early interven-tion of kidney problems for patients with eyes affected first. (Am J Ophthalmol 2023;252: 188-204. (c) 2023 Elsevier Inc. All rights reserved.)