KCNV2相关视锥细胞营养不良患者基因及临床特征  

Clinical and genetic characteristics of patients with KCNV2-associated cone dystrophy

作　　者：朱田 李蕙[1] 王雷 卫星 吴世靖 孙子系 睢瑞芳[1] Zhu Tian;Li Hui;Wang Lei;Wei Xing;Wu Shijing;Sun Zixi;Sui Ruifang(Department of Ophthalmology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Ophthalmology,Beijing Mei'ermu Hospital,Beijing 100063,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院眼科,北京100730 [2]北京美尔目医院眼科,100063

出　　处：《中华实验眼科杂志》2020年第4期312-318,共7页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目(81873687);中国医学科学院医学与健康科技创新工程项目(2016-I2M-1-002);北京市自然科学基金项目(7202159)。

摘　　要：目的分析KCNV2相关视锥细胞营养不良患者的基因及临床特征。方法纳入2017年8月至2019年12月在北京协和医院确诊的3个KCNV2基因相关视锥细胞营养不良家系。采集病史及眼科检查结果,包括视力、色觉、彩色眼底照相、眼底自发荧光(FAF)、光相干断层扫描(OCT)、视野和视网膜电图(ERG)。采集患者及其父母外周血5 ml并提取DNA。利用二代测序(NGS)靶向捕获技术,确诊KCNV2基因变异相关视锥细胞营养不良患者,并进行Sanger验证及家系共分离检测。结果本研究中共确定3例来自不同家系的中国汉族KCNV2基因相关视锥细胞营养不良患者,其中2例患者携带复合杂合变异,1例近亲患者携带纯合变异。共确定5种新发致病变异包括p.T121M、p.R244C、p.C199Y、p.M250R和p.L171Pfs*201。3例患者均为男性,年龄分别为25岁、16岁和2岁,均有双眼视力低下和畏光症状,2例患者存在色觉障碍和眼球震颤,呈牛眼征、金箔样反光等特征性眼底表现。FAF显示黄斑区低荧光伴或不伴周围高荧光环,OCT示黄斑区视网膜变薄,感光细胞层萎缩,年龄较大的患者萎缩范围相对较宽,视野显示中心暗点伴或不伴周边视野缺损,ERG显示视锥系统严重受累,表现为明适应反应振幅严重降低,峰时延长,视杆系统受累情况各异,但均可见暗适应特征性a波基底宽大。结论KCNV2相关视锥细胞营养不良患者具有特征性ERG表现。中国患者ERG表现及基因型与国外患者不同。Objective To access the genetic defects and clinical characteristics of patients with KCNV2-associated cone dystrophy.Methods Three pedigrees with KCNV2-associated cone dystrophy were recruited in Peking Union Medical College Hospital from August 2017 to December 2019.Peripheral blood from each patient and their parents was collected,and genomic DNA was extracted.Targeted exome capture plus next-generation sequencing(NGS)was used to detect the candidate variants.Suspected causative variants were validated by Sanger sequencing and segregation analysis.Comprehensive ocular examinations were performed,including vision acuity,colour vision,fundus photography,fundus autofluorescence(FAF),optical coherence tomography(OCT),visual field and electroretinogram(ERG).This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and adhered to the tenets of the Declaration of Helsinki.Written informed consent was obtained from each patient prior to any medical examination.Results Three probands from three unrelated Chinese families were confirmed carrying biallelic KCNV2 disease-causing variants.Two patients harbored compound heterozygous variants and one patient with history of consanguinity was identified carrying homozygous variant.Five novel variants in the KCNV2 gene were identified,including p.T121M,p.R244C,p.C199Y,p.M250R and p.L171Pfs*201.All patients enrolled in this study were male with age of 25,16 and 2 years old,respectively.Three affected individuals complained of vision loss and photophobia and two patients demonstrated reduced color perception and nystagmus.Macular discoloration(bull's eye maculopathy or gold foil macular reflex)was observed in fundus photographs.Macular hypofluorescence was illustrated in FAF imaging,which accompanying a broad hyperfluorescent ring surrounding the central atrophy or not.Macular thinning with loss of the inner segment ellipsoid zone was noted in OCT images,and the disruption was more profound in older patients.Central scotoma with or withou

关 键 词：KCNV2基因 视锥细胞营养不良 基因突变 二代测序 视网膜电图 

分 类 号：R77[医药卫生—眼科]