Blocker displacement amplification-based genetic diagnosis for autosomal dominant polycystic kidney disease and the clinical outcomes of preimplantation genetic testing

作者全名："Lin, Tingting; Luo, Junfeng; Yu, Haibing; Dong, Bohao; Zhang, Qi; Zhang, Wei; Chen, Ke; Xiang, Yezhou; Liu, Dongyun; Huang, Guoning"

作者地址："[Lin, Tingting; Yu, Haibing; Zhang, Qi; Chen, Ke; Xiang, Yezhou; Liu, Dongyun; Huang, Guoning] Chongqing Med Univ, Ctr Reprod Med, Women & Childrens Hosp, Chongqing, Peoples R China; [Lin, Tingting; Yu, Haibing; Zhang, Qi; Chen, Ke; Xiang, Yezhou; Liu, Dongyun; Huang, Guoning] Chongqing Hlth Ctr Women & Children, Chongqing, Peoples R China; [Lin, Tingting; Zhang, Qi; Huang, Guoning] Chongqing Key Lab Human Embryo Engn, Chongqing, Peoples R China; [Luo, Junfeng; Dong, Bohao] NuProbe China, Shanghai, Peoples R China; [Zhang, Wei] AmCare Genom Lab, Guangzhou, Peoples R China"

通信作者："Liu, DY; Huang, GN (通讯作者)，Chongqing Med Univ, Ctr Reprod Med, Women & Childrens Hosp, Chongqing, Peoples R China.; Liu, DY; Huang, GN (通讯作者)，Chongqing Hlth Ctr Women & Children, Chongqing, Peoples R China.; Huang, GN (通讯作者)，Chongqing Key Lab Human Embryo Engn, Chongqing, Peoples R China."

来源：JOURNAL OF ASSISTED REPRODUCTION AND GENETICS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000932713200001

JCR分区：Q2

影响因子：3.1

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：ADPKD; PKD1; PKD2; Blocker displacement amplification; Preimplantation genetic testing

摘要："ObjectiveGiven that the molecular diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is complicated, we aim to apply blocker displacement amplification (BDA) on the mutational screening of PKD1 and PKD2.MethodsA total of 35 unrelated families with ADPKD were recruited from the Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University (Chongqing, China), from October 2018 to October 2021. Long-range PCR followed by next-generation sequencing were applied for resequencing of PKD1 and PKD2, and the putatively disease-causative variants were verified with BDA. The effects of ADPKD on male and female infertility and the factors influencing the clinical outcomes of preimplantation genetic testing (PGT) for ADPKD were investigated.ResultsA total of 26 PKD1 variants and 5 PKD2 variants were identified, of which 13 were newly discovered. The BDA system worked effectively for eliminating the interference of pseudogenes in genetic testing of PKD1 (1-33 exons) with different concentrations of genome DNA. The females with ADPKD have no specific infertility factors, while 68.2% of the affected men were with abnormal sperm concentration and/or motility with an indefinite genotype-phenotype relationship. As for PGT, the fertilization rate of couples with the male partner having ADPKD was relatively lower compared to those with the female partner being affected. The ADPKD patients receiving PGT usually achieved high rates of live births.ConclusionThese findings expanded the variant spectrum of PKD genes and emphasized the application prospect of blocker displacement amplification on PKD1-related genetic diagnosis."

基金机构：Natural Science Foundation of Chongqing [CSTC2021JCYJ-MSXMX0722]; Chongqing Health Center for Women and Children [2020YJMS01]

基金资助正文：This study was supported by grants from the Natural Science Foundation of Chongqing (CSTC2021JCYJ-MSXMX0722) and the Chongqing Health Center for Women and Children (2020YJMS01).