结晶样视网膜变性患者的基因突变检测

Identification of CYP4V2 gene mutations in patients with Bietti's crystalline dystrophy

目的检测结晶样视网膜变性(BCD)患者的CYP4V2基因突变位点。方法收集临床诊断为BCD患者(先证者)及其家系成员,完善最佳矫正视力、眼底照相、光学相干断层成像技术、电生理及眼底荧光造影等眼科相关检查。同时招募150名无血缘关系的健康志愿者作为健康对照组。采集先证者、先证者家系成员及健康对照组外周血,提取DNA,并进行CYP4V2基因11个外显子的扩增,对扩增产物进行直接测序,确定突变位点。测序结果与健康对照组的基因检测结果进行对照。结果共收集3个BCD家系,均为散发患者,先证者眼底表现为典型的结晶样物质沉积,伴不同程度的脉络膜萎缩,角膜均未累及。DNA测序发现2个家系的先证者存在c.802-8_810dell7insGC(Exon7del)突变,另一家系先证者存在c.219T>A(p.F73L)突变,此外3个家系均检测到c.775C>A(p.Q259K)突变。150名健康志愿者中有32人发现c.775C>A (p.Q259K)突变。结论中国人群BCD患者中最常见c.802-8_810dell7insGC(Exon7del)突变为家系1、家系2的致病突变,此外c.219T>A(p.F73L)突变可能为家系3的致病突变。

Objective To identify CYP4V2 gene mutations in Bietti's crystalline dystrophy(BCD).Methods BCD patients and their family members were recruited for complete clinical ophthalmic examination,including best corrected visual acuity,fundus photography,optical coherence tomography,electrophysiological examination,and fluorescein and indocyanine green angiography.Peripheral blood was taken fromthe probands and their family members to extract the DNA.PCR was used to amplify the target DNA,and direct sequencing was performed to determine the mutations in CYP4V2 gene.A total of 150 healthy volunteers were enrolled as control group.Results Three BCD probands presented with yellow-white shiny crystalline depositing on the posterior pole of the retina and various degree of atrophy of retinal pigment epithelium.Mutation of c.802-8_810dell7insGC(Exon7del)was identified in 2 probands,and mutation of c.219T >A(p.F73L)was identified in 1 proband;while the mutations were not detected in their family members.Mutation c.775C >A(p.Q259K)was found in all three probands and their family members,which was also detected in 32 healthy controls.Conclusion In this study,the most common mutation c.802-8_810dell7insGC(Exon7del)was found in two BCD prosbands,and c.219T >A(p.F73L)may be the causative mutation in one BCD prosband.