全外显子组测序技术对两个眼前节发育不良家系致病基因检测  

Disease genes detection of two anterior segment dysgenesis pedigree by whole exome sequence

作　　者：王凯[1] 张丹 郝朋[1] 王犁明[1] 李宁东[3] 李轩[1] VVANG Kai ZHA-NG Dan HAO Peng WANG Li--Ming LI Ning-Dong LI Xuan

机构地区：[1]天津医科大学眼科临床学院天津市眼科医院天津市眼科研究所天津市眼科学与视觉科学重点实验室,天津市300020 [2]郑州普瑞眼科医院,河南省郑州市450000 [3]首都医科大学附属北京儿童医院,北京市100045

出　　处：《眼科新进展》2017年第3期235-238,243,共5页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(编号:81170884)~~

摘　　要：目的筛查两个眼前节发育不良(anterior segment dysgenesis,ASD)家系的致病基因突变。方法对2个来自河北和河南的ASD家系进行分析。在获得受检者同意后,对家系成员进行详细的眼科检查,采集外周静脉血,提取全基因组DNA。依据测序需求选取家系1中2例患者及1名正常对照、家系2中1例患者及1名正常对照进行全外显子组测序,对测序结果筛选候选基因,运用Sanger测序进行验证。利用Poly Phen-2,SIFT Human Splicing Finder软件进行突变危害性预测。结果家系1连续3代均有患者发病,符合常染色体显性遗传特征,9例患者有均不同程度的双眼ASD。得到13个SNV和55个In Del候选突变,在候选基因PAX6中,家系1发现一已知错义突变c.T2A(p.M1K);家系2中共8名成员,其中2例患者,在测序中发现一已知剪切位点突变c.357+1g>c。3个预测软件作出危害性预测。结论外显子测序技术快速检测出PAX6基因中T2A(p.M1K)和c.357+1g>c突变,并确定其为ASD的致病突变。Objective To identify the disease-causing gene mutation in families with anterior segment dysgenesis （ASD）.Methods Two ASD families coming from Henan and Hebei provinces were enrolled in this study.Ocular examinations were performed,and periphery blood specimens were collected from each family member under the informed consent.The blood samples of 2 patients and 1 normal person in family 1 and 1 patient and 1 normal person in family 2 were analyzed by the whole exome sequences.The candidate genes were verified by Sanger sequence and predicted damages by PolyPhen-2 and SIFT Human Splicing Finder software.Results Family 1 including 9 patients were examined in serial 3 passages,which conformed to autosomal dominant inheritance pattern.Clinical examination revealed binocular anterior segment dysgenesis in the 9 patients.There were 13 SNV and 55 InDel candidate mutations.And missense mutation c.T2A（p.M1K）on PAX6 gene was found.Family 2 included 8 members,and 2 patients were examined.The splicing mutation c.357＋1g〉c on the same gene was found.Conclusion T2A（p.M1K）and c.357＋1g〉c mutations in PAX6 gene are responsible for ASD.Whole exome sequence provides a new approach to detect disease-causing mutation of ASD with diversity clinical phenotypes.

关 键 词：全外显子组测序 眼前节发育不良 PAX6基因 

分 类 号：R773[医药卫生—眼科]