中国一先天性无虹膜家系的遗传分析及PAX6基因突变位点的检测  

Genetic analysis of a Chinese family with congenital aniridia and detection of PAX6 mutation locus

作　　者：张陆希 杨鸽[1] 贾竞[3] 万文萃[1] 杨鑫[1] 金学民[1,2] 

机构地区：[1]郑州大学第一附属医院眼科,450052 [2]河南省立眼科医院河南省眼科研究所 [3]郑州大学基础医学院,450001

出　　处：《中华实验眼科杂志》2017年第8期721-725,共5页Chinese Journal Of Experimental Ophthalmology

摘　　要：背景先天性无虹膜是双眼发病的遗传性疾病，目前的研究表明先天性无虹膜患者配对盒转录因子6（PAX6）基因突变位点具有多样性。目的通过目标序列捕获测序结合一代测序验证技术对1个中国先天性无虹膜家系进行基因突变位点的筛查和遗传分析。方法采用横断面研究方法，本研究组于2016年3月纳入在郑州大学第一附属医院确诊的1个中国汉族先天性无虹膜家系，并对该家系成员进行致病突变基因检测。该家系全体成员均接受神经系统、口服葡萄糖耐量试验等全身体格检查以及眼科相关检查。采集现存家系所有成员前臂静脉血10ml以提取基因组DNA，以先证者基因组DNA为模板行前房角发育异常致病基因的目标基因定点捕获测序分析，经与各基因库比对筛选出候选致病基因位点，采用PCR法对该家系成员行致病基因位点DNA片段扩增，采用Sanger测序技术在该家系除先证者以外的2例患病者和表型正常成员中进行候选致病基因验证。结果该家系共3代9名成员，I1去世，现存8位成员，包括患病者3例（112及其子代Ⅲ1、Ⅲ2）和表型正常者5人，符合常染色体显性遗传模式。所有家系成员未发现神经系统异常，口服葡萄糖耐量试验结果均呈阴性。3例患病者视力均明显下降且不能矫正，眼压平均值为21mmHg（1mmHg=0．133kPa），患者均存在虹膜完全缺如、角膜基质层混浊、眼球水平震颤、黄斑中心凹发育不良症状。此外，Ⅱ2患者存在左眼上睑下垂、右眼先天性白内障表现，Ⅲ2同时存在双眼先天性白内障、双侧晶状体不全脱位。先证者目标序列捕获测序分析及数据库比对显示，所有患病者PAX6基因第6号外显子上碱基替换e．183C〉A，经Sanger测序验证后证实突变基因与表型共分离。结论PAX6基因c．183C〉A突变是该先天性无虹膜家系的致病突变位点。Background Congenital aniridia is a rare bilateral hereditary ophthalmopathy which impact panocular. Researches showed that congenital aniridia can be caused by different mutation locus of PAX6 genes, and the mutations are multifarious. Objective This study was to detect and analyze the mutations of a Chinese family with congenital aniridia by using targeted sequence capture sequencing and direct Sanger sequencing. Methods This study was approved by Ethic Committee of the First Affiliated Hospital of Zhengzhou University and followed Declaration of Helsinki. Written informed consent was obtained from subjects or their custodians before any related medical examination. A cross-sectional study was performed. A Chinese congenital aniridia family was included at the First Affiliated Hospital of Zhengzhou University in March,2016. All the family members received systemic medical examinations including nervous system and oral glucose tolerance test and then the ocular examinations were carried out. The periphery blood of 10 ml was collected from the members for genomic DNA extraction. Targeted sequence capture sequencing was performed on the DNA of proband to screen out the suspicious mutant locus, The mutation was verified by comparing the Sanger direct sequencing results from all family members. Results A total of 3 generations of 9 members were included in this congenital aniridia pedigree, and the Ⅰ 1 was dead without eye abnormality. Three patients （ Ⅱ 2 and her children Ⅲ 1, Ⅲ 2） and 5 normal family members were determined, showing an autosomal dominant inheritance pattern. No abnormal signs were found in nervous system and oral glucose tolerance test in the families. The reduce of visual acuity, ocular hypertension （21 mmHg） , absence of biocular iris, opacification of corneal stroma, horizontal nystagmus, hapoplasia of fovea were found in all the sufferers. In addition, the ptosis of the left eye,congenital cataract of the right eye in I1 2 patient as well as biocular cataract and subluxation of

关 键 词：无虹膜/遗传性 人类第11号染色体/基因 配对盒转录因子6/基因 家系谱 中国人 目标序列捕获测序 无义突变 

分 类 号：R773.1[医药卫生—眼科]