全外显子测序和靶向测序在男性IHH中基因检测效能的比较  

Target gene panel method versus whole-exome sequencing in detection of idiopathic hypogonadotropic hypogonadism in males

作　　者：郭艳菊 郭耀蔓 韩莹 吴秋月 杨阳 罗涛 许晓风[1] 夏欣一 GUO Yan-ju;GUO Yao-man;HAN Ying;WU Qiu-yue;YANG Yang;LUO Tao;XU Xiao-feng;XIA Xin-yi(School of Life Sciences,Nanjing Normal University,Nanjing,Jiangsu 210023,China;PLA Research Institute of Clinical Laboratory Medicine,General Hospital of Eastern Theater Command,Nanjing,Jiangsu 210002,China)

机构地区：[1]南京师范大学生命科学学院,江苏南京210023 [2]东部战区总医院解放军临床检验医学研究所,江苏南京210002

出　　处：《中华男科学杂志》2021年第10期899-903,共5页National Journal of Andrology

基　　金：国家避孕药具不良反应监测中心开放课题(YJJC201802);江苏省人口学会开放课题(JSPA2019020)。

摘　　要：目的:比较靶向基因panel和全外显子测序(WES)在特发性低促性腺激素性性腺功能减退症(IHH)疾病中的检测效能,选择出更适合IHH基因检测方法。方法:选取24种与IHH的分子发病机制密切相关的基因组成基因panel,对73例IHH患者用基因panel检测突变位点,测序结果用sanger测序验证。结合本实验,在数据库中以IHH为关键词检索文献,计算文献中用WES检测IHH疾病的阳性率。比较两种方法检测IHH的阳性率。结果:73例IHH患者用基因panel检测,共检测到7例患者存在致病性突变,其中FGFR1、CHD7、KISS1R各2例,NR5A1 1例,经Sanger测序验证得出,panel测序的阳性率为9.7%。本研究从数据库共搜索到1 336篇相关文献,其中符合纳入标准的有5篇,测序的阳性率约30%。结论:对于突变基因明确的疾病,panel法价格相对便宜,测序深度较高。但是对于遗传模式比较复杂,突变基因不明确的疾病,WES的检测效果更好。IHH这种遗传模式复杂,仍有部分突变基因不明确的疾病,WES和基因panel均适用于致病基因的检测。一线筛查,panel测序更方便,深入研究则是WES方法更适用。Objective: To compare the efficiency of the target gene panel method and whole-exome sequencing(WES) in detecting idiopathic hypogonadotropic hypogonadism(IHH), and select a more suitable gene detection method. Methods: We selected 24 genes closely related to the molecular pathogenesis of IHH to make up the gene panel, detected the mutation sites in 73 patients with IHH using the panel method, and verified the results of sequencing with the Sanger method. Using the key words "idiopathic hypogonadotropic hypogonadism", we searched databases for relevant literature, calculated the positive rate of IHH detected by WES and compared it with that detected with the panel method. Results: Of the 73 cases of IHH detected with the panel method, 7 were found with pathogenic mutations, including 2 cases of FGFR1, 2 cases of CHD7, 2 cases of KISS1R, and 1 case of NR5A1 mutation. Sanger sequencing showed that the positive rate of the panel method was 9.7%. Of the 1 336 articles retrieved, 5 met the inclusion criteria and were included, in which WES revealed a positive rate of about 30%. Conclusion: For detection of the diseases with clear mutated genes, the panel method is relatively inexpensive and has a high sequencing depth, while for detection of the diseases with complicated genetic patterns and unclear mutated genes, WES is more efficient. Further studies are needed for choice of the two methods for different purpose of detection.

关 键 词：特发性低促性腺激素性性腺功能减退症 全外显子测序 基因panel 

分 类 号：R698.2[医药卫生—泌尿科学]