一个视锥-视杆营养不良大家系致病基因的初步鉴定  

Identification of mutated gene in a large pedigree with cone-rod dystrophy

作　　者：陈蕾[1] 顾蕾[2] 顾鸣敏[1] 吴星伟[2] 

机构地区：[1]上海交通大学医学院医学遗传室,上海200025 [2]上海市第一人民医院眼科,上海200080

出　　处：《诊断学理论与实践》2016年第3期235-239,共5页Journal of Diagnostics Concepts & Practice

基　　金：国家自然科学基金(31571295)

摘　　要：目的 :明确一个常染色体显性遗传眼底病大家系中患者的临床特征,找出该家系的致病基因,并进行基因诊断。方法:受累患者接受问诊及各项眼科检查;对先证者进行覆盖372个眼科遗传病基因的外显子测序芯片突变筛查,并对其中的10个可疑突变位点进行Sanger测序及验证。结果:该家系患者均表现出类似进展型视锥-视杆细胞营养不良(cone-rod dystrophy,CORD)的特征,且起病较早,症状较重。外显子测序分析发现,在患者视锥-视杆同源盒(cone-rod homeobox,CRX)基因的第3个外显子上存在一个错义突变(c.238G>A),导致该基因编码蛋白第80位的谷氨酸变成赖氨酸。结论:本研究首次在黄种人中发现一个CRX[c.238G>A(p.E80K)]基因突变的CORD大家系,同时提示由该基因突变所致CORD患者的临床表现比p.E80A及p.E80Q所致患者更为严重。Objective To investigate the clinical manifestations of a large Chinese family presenting with autosomal dominant hereditary retinopathy, and to identify the pathogenic gene. Methods Interrogation and ophthalmological examinations were performed in all the affected members. Three hundred and seventy-two exons in ophthalmic diseaseassociated genes were sequenced with Illumina Hi Seq 2000 platform. Ten highly suspected mutation sites were sequenced and verified with Sanger sequencing. Results All affected members presented manifestations of progressive cone-rod dystrophy, with early-onset and serious symptoms. A missense mutation in exon 3（c.238G〉A） of CRX gene was identified,resulting in an amino acid change from glutamic acid to lysine（E80K）. Conclusions This is the first report of CRX mutation（p.E80K） pedigree in yellow race, and it revealed that manifestations of patients with mutation in p.E80 K were more serious than those with mutation in p.E80 A and p.E80 Q.

关 键 词：视锥-视杆营养不良 视锥-视杆同源盒 E80K 外显子测序 

分 类 号：R774.1[医药卫生—眼科]