利用外显子组测序技术识别先天性输精管缺如新基因

Congenital absence of the vas deferens (CAVD) is a kind of congenital malformation of the male reproductive system that can be one of the most important reason for the obstructive azoospermia and male infertility. Up to now, only one causal gene of CAVD has been identified, that is cystic fibrosis transmembrane conductance regulator (CFTR) gene, but the mutation of CFTR gene can't explain all etiology and clinical features of CAVD. We have already established cohorts of one type of CAVD, congenital bilateral absence of the vas deferens (CBAVD) in the Han Chinese population and screened CFTR gene to exclude mutation carriers (44 of 73 CAVD samples have been identified CFTR gene mutation). In this project, in order to identify new pathogenic genes of CAVD, we plan to use whole exome sequencing technique to capture and sequence all exons of 29 CBAVD patients after excluding CFTR mutations. Moreover, to replicate and confirm the reliability of the new identified genes, we will sequence 300 patients with CAVD as a replication data set of this project. Our result will identify not only new causal gene and reveal the etiology of CAVD, but also can be theoretical basis for genetic consultation, genetic therapy, and early intervention in patients with CAVD.

先天性输精管缺如(CAVD)是男性生殖系统的一种先天性畸形，是阻塞性无精子症及男性不育的重要病因之一。目前已知唯一的CAVD致病基因CFTR的基因变异不能够解释全部CAVD发病的遗传风险与临床特征。本研究是基于本课题组前期研究偶，在针对中国汉族人群先天性双侧输精管缺如（CBAVD）患者CFTR基因突变谱系统分析工作基础上，拟利用高通量全外显子组测序技术，对不携带CFRT变异位点的29例CBAVD患者进行新的致病基因筛查；对初步确定的潜在致病基因，在300例各种类型CAVD样本中进行验证测序，进一步确定其致病性。本研究有望发现新的CAVD相关基因，为阐明CAVD发病机制提供新的思路，并为CAVD患者的遗传咨询、基因治疗、早期干预等领域提供理论支持。

先天性输精管缺如(CAVD)是男性生殖系统的一种先天性畸形，是阻塞性无精子症及男性不育的重要病因之一。已知唯一的CAVD致病基因CFTR的基因变异不能够解释全部CAVD发病的遗传风险与临床特征。本研究是扩大收集样本，针对中国汉族人群先天性双侧输精管缺如（CBAVD）患者CFTR基因突变谱系统分析工作基础上，利用高通量全外显子组测序技术，对CBAVD患者进行新的致病基因筛查并鉴定ADGRG2基因罕见变异对CBAVD的贡献；此外，通过对多年临床数据进行回溯，挖掘全部高发家系，并对高发家系的患者全外显子技术，识别鉴定了CFTR基因新的致病模式。本研究验证了中国人新的CBAVD基因及CFTR罕见变异新的致病模式，为阐明CAVD发病机制提供新的思路，并为CAVD患者的遗传咨询、基因治疗、早期干预等领域提供理论支持。