成人先天性单肾缺如患者Fraser基因谱突变筛查  

Screening of Fraser genetic spectrum mutation with targeted gene capture sequencing in congenital unilateral renal agenesis

作　　者：徐倩[1] 王朝晖[1] 吴杭迪 谢静远[1] 张文[1] 俞海瑾[1] 王伟铭[1] 钱莹[1] 章倩莹[1] 乔盼盼[1] 唐永华[2] 陈楠[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院肾脏科,上海200025 [2]上海交通大学医学院附属瑞金医院放射科,上海200025

出　　处：《内科理论与实践》2016年第5期290-295,共6页Journal of Internal Medicine Concepts & Practice

基　　金：国家自然科学基金项目(项目编号:81170634)

摘　　要：目的:利用目的基因捕获测序技术对先天性单肾缺如(URA)患者进行致病基因筛查,并对临床表型进行相关分析。方法:2008年1月至2016年1月对我院81例无血缘关系汉族成人URA患者进行FRAS1、FREM1及FREM2基因外显子测序,对检出的变异位点进行Sanger法测序验证,并在100名正常汉族人群中验证。结果:共发现18例患者在该3种基因上存在18种致病突变,包括15种错义突变和3种插入/缺失突变,共计19例次。其中,FRAS1基因10例患者发生9种突变、FREM1基因4例发生4种突变、FREM2基因5例发生5种突变,有1例患者同时发生1种FRAS1基因突变和1种FREM2基因突变。临床分析发现携带突变组患者左侧肾脏缺失比例大于未携带组(77.8%比42.9%,P=0.009),其余临床特征均无明显差异。结论:FRAS1、FREM1、FREM2基因是URA常见的致病基因。FRAS1、FREM1及FREM2基因杂合错义突变可能是其常见致病类型,发生该3种基因突变患者更易出现左侧肾脏缺如,但并不引起其余临床表现的差异。Objective To screen the pathogenic gene mutation with targeted gene capture sequencing and analysis the correlation with clinical phenotypes in adult patients with congenital unilateral renal agenesis（URA）. Methods Eighty one URA patients from January 2008 to January 2016 were enrolled in this study and 100 healthy subjects were served as controls. The exons of FRAS1（Fraser extracellular matrix complex subunit 1）, FREM1（FRAS1 related extracellular matrix protein 1） and FREM2 gene mutation were screened by targeted gene capture sequencing and the mutations detected were confirmed by Sanger sequencing. Demographic and baseline clinical data were recorded and analyzed. Results Of the 81 URA patients, 18 different pathogenic mutations were found in 18 patients, 15 were missense mutation and 3 were in-sertion/delation mutation; the total number of mutation was 19. Nine pathogenic mutations of FRAS1 gene were found in 10 patients, 4 pathogenic mutations of FREM1 gene were found in 4 patients, and 5 pathogenic mutations of FREM2 gene were found in 5 patients. One patient had both FRAS1 and FREM2 mutations. Analysis of correlation with clinical characteristics showed that left renal agenesis occurred more commonly in mutation carriers than in non-carriers（77.8%vs. 42.9%, P =0.009）; other clinical parameters between the two groups showed no significant difference. Conclusions FRAS1, FREM1 and FREM2 might be the commonly seen pathogenic genes in Chinese URA patients. Our results indicated that missense mutations in Fraser genetic spectrum could cause isolated URA. Patients with mutations in Fraser gene spectrum more frequently had left renal agenesis, but having no significant differences in other clinical manifestations.

关 键 词：先天性单肾缺如 致病基因 FRAS1基因 FREM1基因 FREM2基因 

分 类 号：R692[医药卫生—泌尿科学]