Hongbo Cheng1,2, Shenmin Yang2, Qingxia Meng2, Bo Zheng2, Yidong Gu2, Luyun Wang2, Tao Song3, Chunlu Xu3, Gaigai Wang2, Mutian Han2, Liyan Shen2, Jie Ding2, Hong Li4, Jun Ouyang5. 1. Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China. 2. Center for Reproduction and Genetics, NHC Key Laboratory of Male Reproduction and Genetics, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China. 3. Department of Andrology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China. 4. Center for Reproduction and Genetics, NHC Key Laboratory of Male Reproduction and Genetics, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China. hongliszivf@163.com. 5. Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China. 381174664@qq.com.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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.
Authors: A Gaikwad; S Khan; S Kadam; K Kadam; V Dighe; R Shah; V Kulkarni; R Kumaraswamy; R Gajbhiye Journal: Andrologia Date: 2017-08-03 Impact factor: 2.775
Authors: Manon S Oud; Liliana Ramos; Moira K O'Bryan; Robert I McLachlan; Özlem Okutman; Stephane Viville; Petra F de Vries; Dominique F C M Smeets; Dorien Lugtenberg; Jayne Y Hehir-Kwa; Christian Gilissen; Maartje van de Vorst; Lisenka E L M Vissers; Alexander Hoischen; Aukje M Meijerink; Kathrin Fleischer; Joris A Veltman; Michiel J Noordam Journal: Hum Mutat Date: 2017-09-06 Impact factor: 4.878