眼科学报2024，Vol.39Issue(8)：381-394,14.DOI:10.12419/24072402
基于高通量测序分析鉴别视网膜病变中的神经纤维瘤病
Identification of neurofibromatosis in retinopathy based on high-throughput sequencing analysis
摘要
Abstract
Objective:To identify neurofibromatosis in retinopathy through high-throughput sequencing analysis and provide important indicators for early diagnosis and treatment.Methods:Variants in NF1 and NF2 were selected from in-house high-throughput sequencing,including targeted exome sequencing,exome sequencing and whole genome sequencing,of individuals with different eye conditions.Pathogenic or likely pathogenic variants were assessed according to ACMG/AMP criteria.All the available clinical data,including clinical manifestation,family history and other examination results,were summarized and further analyzed to determine whether neurofibromatosis.Results:Based on the results of in-house high-throughput sequencing,a total of ten pathogenic or likely pathogenic variants in NF1 and NF2 were identified in 11 unrelated cases with various eye conditions,including three NF2 variants in four cases and seven NF1 variants in seven cases.The unrelated cases with NF1 and NF2 variants had initial clinical manifestation similar to familial exudative vitreoretinopathy(FEVR),macular or retinal dystrophy,strabismus,retinitis pigmentosa,Coats disease,or morning glory syndrome.In one of these cases,who was diagnosed as FEVR at the initial visit,three pathogenic variants of three different genes were identified,namely NF2:c.122G＞A/p.(W41*),RS1:c.520C＞T/p.(R174W)and NYX:c.1027C＞T/p.(R343C).Follow-up examination on this case revealed a complex retinopathy,which were consistent with clinical presentations due to pathogenic variants in NF2,RS1,and NYX,as well as bilateral vestibular schwannomas,spinal ependymoma and multiple schwannomas by MRI.In addition to this patient,a follow-up examination on four of the seven cases present Café-au-lait macules or freckling,which could be easily neglected if neurofibromatosis is not realized on the initial visit,while one had neurofibromatosis in cerebellum.Conclusions:Complex retinopathy may present as the initial sign of neurofibromatosis,and high-throughput sequencing analysis for neurofibromatosis related genes contribute to early diagnosis of neurofibromatosis and facilitating early identification of vital systemic complication.关键词
神经纤维瘤病/NF1/NF2/高通量测序/视网膜病变Key words
neurofibromatosis/NF1/NF2/high-throughput sequencing/retinopathy分类
医药卫生引用本文复制引用
欧阳嘉敏,高阳,易珍,蒋奕,黎仕强,肖学珊,贾小云,张清炯,孙文敏..基于高通量测序分析鉴别视网膜病变中的神经纤维瘤病[J].眼科学报,2024,39(8):381-394,14.基金项目
国家自然科学基金面上项目(82171056) （82171056）
广东省区域联合基金-青年基金项目(2022A1515111060) （2022A1515111060）
广州市科技计划项目(SL2024A03J00525) （SL2024A03J00525）
眼科学国家重点实验室专项经费.This work was supported by the National Natural Science Foundation of China(82171056) （82171056）
the Guangdong Basic and Applied Basic Research Foundation(2022A1515111060) （2022A1515111060）
the Science and Technology Planning Projects of Guangzhou(SL2024A03J00525) （SL2024A03J00525）
the Fundamental Research Funds of the State Key Laboratory of Ophthalmology. （）
