Abstract：
OBJECTIVE: Congenital bilateral absence of the vas deferens (CBAVD) is a major cause of obstructive azoospermia and male factor infertility. CBAVD is mainly caused by mutations in the genes encoding CFTR (cystic fibrosis transmembrane conductance regulator) and ADGRG2 (adhesion G protein-coupled receptor G2). This study aimed to describe CFTR and ADGRG2 variations in 46 Chinese CBAVD patients and evaluated sperm retrieval and assisted reproductive technology outcomes.
METHODS: The CFTR and ADGRG2 genes were sequenced and analyzed by whole-exome sequencing (WES), and variations were identified by Sanger sequencing. Bioinformatic analysis was performed. We retrospectively reviewed the outcomes of patients undergoing sperm retrieval surgery and intracytoplasmic sperm injection (ICSI).
RESULTS: In total, 35 of 46 (76.09%) patients carried at least one variation in CFTR, but no copy number variants or ADGRG2 variations were found. In addition to the IVS9-5 T allele, there were 27 CFTR variations, of which 4 variations were novel and predicted to be damaging by bioinformatics. Spermatozoa were successfully retrachieved in 46 patients, and 39 of the patients had their own offspring through ICSI.
CONCLUSIONS: There are no obvious hotspot CFTR mutations in Chinese CBAVD patients besides the IVS9-5 T allele. Therefore, WES might be the best detection method, and genetic counseling should be different from that provided to Caucasian populations. After proper counseling, all patients can undergo sperm retrieval from their epididymis or testis, and most of them can have their own children through ICSI.
METHODS: The CFTR and ADGRG2 genes were sequenced and analyzed by whole-exome sequencing (WES), and variations were identified by Sanger sequencing. Bioinformatic analysis was performed. We retrospectively reviewed the outcomes of patients undergoing sperm retrieval surgery and intracytoplasmic sperm injection (ICSI).
RESULTS: In total, 35 of 46 (76.09%) patients carried at least one variation in CFTR, but no copy number variants or ADGRG2 variations were found. In addition to the IVS9-5 T allele, there were 27 CFTR variations, of which 4 variations were novel and predicted to be damaging by bioinformatics. Spermatozoa were successfully retrachieved in 46 patients, and 39 of the patients had their own offspring through ICSI.
CONCLUSIONS: There are no obvious hotspot CFTR mutations in Chinese CBAVD patients besides the IVS9-5 T allele. Therefore, WES might be the best detection method, and genetic counseling should be different from that provided to Caucasian populations. After proper counseling, all patients can undergo sperm retrieval from their epididymis or testis, and most of them can have their own children through ICSI.
摘要：
目的：先天性双侧输精管缺失（CBAVD）是梗阻性无精子症和男性因素不育的主要原因。CBAVD主要由编码CFTR（囊性纤维化跨膜传导调节因子）和ADGRG2（粘附G蛋白偶联受体G2）的基因突变引起。本研究旨在描述46例中国CBAVD患者的CFTR和ADGRG2变化，并评估精子回收和辅助生殖技术结果。
方法：通过全外显子组测序（WES）对CFTR和ADGRG2基因进行测序和分析，并通过Sanger测序鉴定变异。进行生物信息学分析。我们回顾性回顾了接受精子提取手术和胞浆内单精子注射（ICSI）的患者的结局。
结果：总计，46例患者中有35例（76.09%）携带至少一种CFTR变异，但没有发现拷贝数变异或ADGRG2变异。除了IVS9-5T等位基因，有27个CFTR变体，其中4个变异是新颖的，被生物信息学预测是有害的。在46例患者中成功进行了精子重建，39名患者通过ICSI有了自己的后代。
结论：中国CBAVD患者中除IVS9-5T等位基因外，无明显热点CFTR突变。因此,WES可能是最好的检测方法，和遗传咨询应该不同于提供给高加索人群。经过适当的咨询，所有患者都可以从附睾或睾丸中取出精子，他们中的大多数人可以通过ICSI拥有自己的孩子。
方法：通过全外显子组测序（WES）对CFTR和ADGRG2基因进行测序和分析，
结果：总计，
结论：中国CBAVD患者中除IVS9-5T等位基因外，无明显热点CFTR突变。
