原发性开角型青光眼家系致病基因检测及其启动子区域甲基化的关系  

Pathogenic genes in families with primary open angle glaucoma and the effect of promoter region methylation

作　　者：李思媛[1] 郑娟 翟玉喜[1] 顾明亮[2] 高建鲁[1] Li Siyuan;Zheng Juan;Zhai Yuxi;Gu Mingliang;Gao Jianlu(Department of Liaocheng People's Hospital,Liaocheng 252000,China;Department of Beijing Institute of Genetics,Chinese Academy of Sciences,Beijing 100101,China)

机构地区：[1]山东省聊城市人民医院,252000 [2]中国科学院北京基因研究所

出　　处：《临床眼科杂志》2021年第1期1-4,共4页Journal of Clinical Ophthalmology

基　　金：山东省自然科学基金(ZR2015HL053);山东省自然科学基金面上项目(ZR2019PH050)。

摘　　要：目的确定原发性开角型青光眼(POAG)一家系致病基因,并初步探讨该致病基因甲基化在POAG发病中的作用。方法收集POAG一个家系,整理其病史和眼科相关检查资料,采集家系成员血样,应用基因芯片对该家系进行致病基因的染色体定位,通过甲基化测序检测致病基因启动子区域的甲基化程度。结果该家系共五代81例,生存78例,患者10例。患者均可见眼压升高、视神经损伤和典型青光眼视野缺损,在发病时间上具有迟发性。我们发现在rs10911021的位置有一个与青光眼候选基因重叠的连锁峰,其LOD值为3.302,NPL值为16.67,在MYOC G1099A鉴定出致病突变(G367R),甲基化测序显示该致病基因启动子甲基化在疾病各亚组之间分布无明显差异。结论MYOC G1099A为POAG家系的致病突变,其迟发性可能与致病基因启动子甲基化无关。Objective To identify pathogenic genes in a pedigree with primary open angle glaucoma(POAG),and to preliminarily explore the role of its methylation in the pathogenesis of POAG.Methods The medical history and ophthalmic examination results,as well as blood samples were collected from a pedigree of POAG.The localization of pathogenic genes was performed by gene chips,and the methylation degree of the promoter region in the pathogenic genes was detected by methylation sequencing.Results There were 81 people in five generations of the family,with 78 alive and 10 POAG patients.Elevated intraocular pressure,optic nerve injury and typical visual field defect can be seen in all POAG patients,who were all late-onset POAG.We found a linkage peak at rs10911021 which overlapped with glaucoma candidate genes,with an LOD value of 3.302 and a NPL value of 16.67.Pathogenic mutation(G367R)was identified in MYOC G1099A.Methylation sequencing showed that the methylation degree of the promoter in the pathogenic gene was not significantly different among various subgroups of the disease.Conclusions MYOC G1099A is a pathogenic mutation for this POAG pedigree,and the late onset of disease may not be related to methylation of the promoter in this pathogenic gene.

关 键 词：原发性开角型青光眼 基因芯片 甲基化测序 迟发性 

分 类 号：R73[医药卫生—肿瘤]