State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, SunYat-Sen University, Guangzhou, China.
Invest Ophthalmol Vis Sci. 2019 Jun 3;60(7):2659-2666. doi: 10.1167/iovs.19-26619.
The purpose of this study was to investigate the genetic mutation spectrum in Chinese patients with familial exudative vitreoretinopathy-associated rhegmatogenous retinal detachment (FEVR-RRD) and to analyze the preliminary genotype-phenotype association.
In this consecutive, cross-sectional study, 54 patients with FEVR-RRD were studied. Comprehensive ophthalmic examinations and targeted next-generation sequencing were performed in all patients. The genotype-phenotype association was also analyzed.
Causative mutations were identified in 38.9% (21/54) of patients (14/54 in LRP5, 4/54 in FDZ4, and 3/54 in TSPAN12). The study identified 22 potentially pathogenic mutations in 21 unrelated FEVR probands, and 14 were novel (10/15 in LRP5, 1/4 in FZD4, and 3/3 in TSPAN12). Furthermore, to explore the genotype-phenotype association, late-phase angiographic posterior and peripheral leakage (LAPPEL) was identified in 100% (4/4) of patients with FZD4 mutations and 100% (3/3) of patients with TSPAN12 mutations but only in 42.9% (6/14) of patients with LRP5 mutations. Extraretinal neovascularization (ERNV) was found in 100% (4/4) of patients with FZD4 mutations and in 66.7% (2/3) of patients with TSPAN12 mutations, but only in 21.4% (3/14) of patients with LRP5 mutations.
The positive rate for pathogenic mutations in the known FEVR-associated genes was 38.9% (21/54). Among the mutations, LRP5 mutation was the predominant, accounting for 66.7% (14/21) of genetic positive patients. Patients with FEVR-RRD due to LRP5 mutations have less retinal vascular leakage or neovasculization than do patients with FEVR-RRD due to TSPAN12/FZD4 mutations. Moreover, 14 novel variants were found, which provided a deeper understanding of this disease.
本研究旨在调查中国家族性渗出性玻璃体视网膜病变相关性孔源性视网膜脱离（FEVR-RRD）患者的基因突变谱，并分析初步的基因型-表型相关性。
在这项连续的、横断面研究中，研究了 54 例 FEVR-RRD 患者。对所有患者进行全面的眼科检查和靶向下一代测序。还分析了基因型-表型相关性。
在 38.9%（54 例中的 21 例）患者中发现了致病突变（54 例中的 14 例 LRP5、4 例 FDZ4 和 3 例 TSPAN12）。该研究在 21 名无关的 FEVR 先证者中发现了 22 个潜在的致病性突变，其中 14 个是新的（15 个 LRP5、4 个 FDZ4 和 3 个 TSPAN12）。此外，为了探讨基因型-表型相关性，发现 FZD4 突变患者的晚期相血管造影后和周边渗漏（LAPPEL）为 100%（4/4），TSPAN12 突变患者为 100%（3/3），而 LRP5 突变患者仅为 42.9%（6/14）。发现 FZD4 突变患者的视网膜外新生血管（ERNV）为 100%（4/4），TSPAN12 突变患者为 66.7%（2/3），而 LRP5 突变患者仅为 21.4%（3/14）。
已知 FEVR 相关基因的致病性突变阳性率为 38.9%（54 例中的 21 例）。在这些突变中，LRP5 突变是主要的，占遗传阳性患者的 66.7%（14/21）。LRP5 突变导致的 FEVR-RRD 患者的视网膜血管渗漏或新生血管形成少于 TSPAN12/FZD4 突变导致的 FEVR-RRD 患者。此外，还发现了 14 个新的变异体，这为深入了解该疾病提供了依据。
