Bietti结晶样视网膜变性的临床表现和基因研究  

Clinical manifestation and gene mutation of Bietti crystalline corneoretinal dystrophy

作　　者：郭彤[1] 贾睿璇 陈宁宁 杨丽萍[1] Guo Tong;Jia Ruixuan;Chen Ningning;Yang Liping(Department of Ophthalmology,Peking University Third Hospital,Beijing Key Laboratory of Restoration of Damaged Ocular Nerve,Beijing 100191,China)

机构地区：[1]北京大学第三医院眼科,眼部神经损伤的重建保护与康复北京市重点实验室,100191

出　　处：《中华实验眼科杂志》2019年第9期730-735,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金面上项目(81770966)。

摘　　要：目的对Bietti结晶样视网膜变性(BCD)家系的临床特征和CYP4V2基因突变位点进行分析总结。方法对2010—2018年在北京大学第三医院眼科确诊为BCD的173个家系共234例患者进行全面的眼科检查,观察其病变特征;抽取患者外周静脉血,提取基因组DNA,采用Sanger测序或高通量测序分析CYP4V2基因的突变。结果典型的BCD患者眼底呈现黄白色结晶样物质沉积,但部分晚期患者结晶样沉积减少或消失,易误诊为其他遗传性视网膜变性。本研究中49个BCD家系先证者初诊时误诊为其他遗传性视网膜变性,误诊率为28.3%。基因诊断结果显示,161例患者携带CYP4V2基因突变,阳性率为93.1%,其中8个为新发现的突变位点,3个已知突变位点c.802-8_810del17bp、c.1091-2A>G和c.992A>C在本研究中出现的频率最高,共占73.5%,是中国汉族BCD患者的突变热点。结论BCD患者具有较特异的眼底改变,但疾病晚期容易误诊,分子诊断可协助疾病的临床诊断。单一的杂合突变不足以导致BCD,CYP4V2基因与BCD的发生未表现出明显的基因型-表型相关性。Objective To analyze the clinical manifestation and CYP4V2 mutations of Bietti crystalline corneoretinal dystrophy(BCD)families.Methods Total of 234 patients(173 families)diagnosed as BCD were recruited in Peking University Third Hospital from 2010 to 2018.All of the subjects underwent comprehensive eye examinations to observe the clinical manifestations.Blood samples were collected and genomic DNA was extracted.The Sanger sequencing or high-throughput sequencing was applied for CYP4V2 gene mutation analysis.This study was approved by the Ethics Committee of Peking University Third Hospital(NO.2012093).All patients and their family members signed informed consent.Results Some patients manifested the typical phenotype of BCD characterized by yellowish-white crystalline deposits throughout the fundus.However,some patients in advanced stage were easily misdiagnosed as other inherited retinal degeneration because the crystalline deposits diminished or even disappeared.Forty-nine probands in our cohort were misdiagnosed as other inherited retinal degeneration at first visit,with a misdiagnosis rate of 28.3%.Genetic diagnosis results showed that 161 patients carried CYP4V2 mutation,and the positive rate was 93.1%.Eight novel mutations were obtained.The three known mutations c.802-8_810del17bp,c.1091-2 A>G and c.992 A>C accounted for 73.5%of the mutations,which were hotspots in Chinese Han populations for BCD.Conclusions Patients with BCD have characteristic fundus manifestation,but are easily misdiagnosed in advanced stage.Molecular diagnosis is valuable in clinical diagnosis of the disease,thus contribute to the prevention and treatment of the disease.A single hybrid mutation is not enough to lead to BCD.No apparent genotype-phenotype correlation between the CYP4V2 gene and occurrence of BCD is identified.

关 键 词：基因突变 Bietti结晶样视网膜变性 CYP4V2基因 

分 类 号：R73[医药卫生—肿瘤]