携带CYP4V2基因突变的结晶样视网膜色素变性患者的表型特征

Clinical features of Bietti crystalline corneoretinal dystrophy caused by mutations in the CYP4V2 gene

目的分析国人结晶样视网膜色素变性(BCD)患者CYP4V2基因型及表型特征。设计回顾性病例系列。研究对象北京同仁医院结晶样视网膜色素变性患者138例。方法回顾患者病历记录及眼科检查结果。先证者、直系亲属及家系患病成员采集外周静脉血,Sanger测序及实时定量荧光PCR检测先证者CYP4V2基因突变,并对致病性突变进行家系共分离验证。主要指标最佳矫正视力、眼前节及眼底情况、CYP4V2基因突变。结果138例BCD患者均携带CYP4V2基因双突变,突变c.802-810del17insCG、c.1091-2A>G和p.H331P是本组患者的常见突变。患者平均最佳矫正视力(LogMAR)(1.17±0.95),平均发病年龄(29.19±9.64)岁,视力损伤程度与病程相关,不受发病年龄影响。所有患者眼底均可见细小颗粒状黄白色结晶沉积,结晶沉积范围及密度随病程而加重。结论本研究拓展了BCD致病基因CYP4V2突变谱,BCD患者临床特征明显,结合多种影像学检查方法可有效进行诊断,致病基因突变的确定可为患者提供相应的遗传咨询帮助。

Objective To analyze mutations of CYP4V2 gene in a cohort of patients with Bietti crystalline corneoretinal dystrophy(BCD)and their clinical features.Design Retrospective case series.Participants 138 unrelated Chinese patients diagnosed with BCD in Beijing Tongren Hospital.Methods All study participants underwent a detailed ophthalmological examinations,mutational screening of CYP4V2 gene was examined via directional Sanger sequencing and real-time quantitative PCR.Main Outcome Measures Visual acuity,slit-lamp biomicroscopy,fundus photography,mutations of CYP4V2 gene.Results All patients were identified CYP4V2 mutation,the most frequent mutation in this cohort were c.802-810del17insCG,c.1091-2A>G and p.H331P.The average best corrected visual acuity(LogMAR)was 1.17±0.95 and average age of onset was 29.19±9.64 years old.The degree of visual impairment was related to the course of disease but not affected by the age of onset.Fundus photograph of all patients revealed typical crystalline deposits,the range and density of it was related to the course of disease.Conclusion Our findings expand the spectrum of CYP4V2 mutation.The clinical characteristic of BCD is obvious,and it could be effectively diagnosed with image manifestation methods.Identification of mutation gene lays foundation for provision of genetic consultation for BCD patients.