BBS基因突变致无色素性的色素性视网膜炎临床表型和基因型分析  

Clinical phenotype and genotype analysis of retinitis pigmentosa sine pigmento caused by BBS gene mutations

作　　者：陈子杰 陶宇菲 王云[3] 黄钦钰 杨明民 刘旭阳 樊宁[3] Chen Zijie;Tao Yufei;Wang Yun;Huang Qinyu;Yang Mingmin;Liu Xuyang;Fan Ning(Xiamen Eye Center,Xiamen University,Xiamen 361000,China;The Second Clinical Medical College,Jinan University,Shenzhen 518040,China;Shenzhen Eye Hospital,Shenzhen Eye Medical Center,Southern Medical University,Shenzhen 518040,China)

机构地区：[1]厦门大学附属厦门眼科中心,厦门361000 [2]暨南大学第二临床医学院,深圳518040 [3]深圳市眼科医院南方医科大学深圳眼科医学中心,深圳518040

出　　处：《中华眼底病杂志》2025年第3期178-185,共8页Chinese Journal of Ocular Fundus Diseases

基　　金：国家自然科学基金(82271087、82070963);深圳市科技计划项目(KCXFZ20230731093359004);福建省自然科学基金(2023J011586、2023J011579);厦门市医疗卫生科技计划项目(3502Z202374100)。

摘　　要：目的观察分析无色素性的色素性视网膜炎(RPSP)致病基因类型及临床表型特征。方法回顾性临床研究。分别于2022年12月在厦门大学附属厦门眼科中心、2023年7月在深圳市眼科医院就诊的2个RPSP家系中2例患者(先证者)及其5名家系成员纳入研究。2个家系无血缘关系,均为汉族。详细询问患者病史并行眼底彩色照相、眼底自发荧光(FAF)、全视野视网膜电图(ff-ERG)检查。采集所有参与者外周静脉血,提取2例患者外周血中基因组DNA。采用全外显子高通量测序技术筛选致病基因及其位点。通过Sanger测序技术筛选家系成员的特定变异位点,并进行家系共分离验证。根据美国医学遗传学与基因组学学会(ACMG)相关遗传变异分类标准与指南对候选变异进行致病性评估。结果2例先证者均为男性,年龄分别为9、7岁。分别以双眼视力差6、3年,弱视治疗效果不佳为主诉就诊。家系1先证者(Ⅱ2),视盘颜色淡红色;后极部豹纹状改变,视网膜动脉较细。FAF检查,黄斑区血管弓外斑驳状荧光减弱;ff-ERG检查,双眼明适应或暗适应均未记录到明显波形。双足6趾畸形,肾囊肿,体型偏胖。临床诊断为双眼RPSP。家系2先证者(Ⅱ1),暗环境下双眼视力较差。视盘鼻侧萎缩灶,豹纹状眼底改变。FAF检查,黄斑中心凹荧光不均匀增强。ff-ERG检查,明适应、暗适应重度异常,b波振幅和潜伏期重度下降、延迟。追问病史,全身检查未发现明显异常。临床诊断为双眼RPSP。2个家系的家系成员眼部及全身检查均未见明显异常。基因检测结果显示,家系1先证者(Ⅱ2)携带BBS2基因c.534+1G>T(M1)纯合变异,为剪接位点变异。其父亲(Ⅰ1)、母亲(Ⅰ2)携带M1杂合变异。结合临床表现和基因检测结果,最终诊断为Bardet-Biedl综合征(BBS)。家系2先证者(Ⅱ1)携带BBS7基因c.950T>G(p.Leu317Arg)(M2)错义变异和c.849+1G>C(M3)剪接位点变异。其父亲(Ⅰ1)、�ObjectiveTo observe and analyze the pathogenic genes and clinical phenotype characteristics of retinitis pigmentosa sinepigmento(RPSP).MethodsA retrospective clinical study.Two patients(proband)and five family members from two RPSP families admitted to Xiamen Eye Center of Xiamen University in December 2022 and Shenzhen Eye Hospital in July 2023 were included in the study.Two families have no blood relationship and were both Han Chinese.Detailed ocular and systemic medical history and specialized examinations were performed for all members,including color fundus photography,fundus autofluorescence(FAF),and full field electroretinogram(ff-ERG)examination.The peripheral venous blood of all members was collected,and genomic DNA was extracted.Pathogenic genes and their loci were screened using whole exome high-throughput sequencing technology.Sanger sequencing was used to verify the pathogenic genes in the two pedigrees.The pathogenicity of candidate variants was evaluated according to the American Society for American College of Medical Genetics and Genomics(ACMG)classification criteria and guidelines for genetic variants.ResultsThe two probands were male,aged 9 and 7 years,respectively.The main complaint was poor binocular vision for 6 and 3 years and poor treatment effect of amblyopia.The proband(Ⅱ2)in family 1 had a pale red color on the optic disc,with leopard-like changes in the posterior pole and thinner retinal arteries.FAF showed mottled fluorescence attenuation outside the macular vascular arch.There was no significant waveform in both bright and dark visual responses of ff-ERG.He also had 6-toed deformity of both feet,renal cysts,and a slightly overweight body.The clinical diagnosis was non-pigmentary retinitis pigmentosa.The proband of family 2(Ⅱ1)had poor binocular vision in a dark environment and had atrophy lesions on the nasal side of the optic disc and leopard print like changes in the fundus.FAF showed uneven enhancement in the fovea.ff-ERG showed severe abnormalities in dark and light response,

关 键 词：BBS7基因 BBS2基因 色素性视网膜炎 BARDET-BIEDL综合征 

分 类 号：R73[医药卫生—肿瘤]