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Updated: Nov 12, 2025
Pre-Implantation Genetic Testing for Aneuploidy on a Semiconductor Based Next-Generation Sequencing Platform
Published on: August 17, 2022
Targeted next-generation sequencing panel screening of 668 Chinese patients with non-obstructive azoospermia
Miao An1, Yidong Liu1, Ming Zhang1
1Department of Urology and Andrology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, People's Republic of China.
Purpose:
We aimed (1) to determine the molecular diagnosis rate and the recurrent causative genes of patients with non-obstructive azoospermia (NOA) using targeted next-generation sequencing (NGS) panel screening and (2) to discuss whether these genes help in the prognosis for microsurgical testicular sperm extraction (micro-TESE).
Methods:
We used NGS panels to screen 668 Chinese men with NOA. Micro-TESE outcomes for six patients with pathogenic mutations were followed up. Functional assays were performed for two NR5A1 variants identified: p.I224V and p.R281C.
Results:
Targeted NGS panel sequencing could explain 4/189 (2.1% by panel 1) or 10/479 (2.1% by panel 2) of the patients with NOA after exclusion of karyotype abnormalities and Y chromosome microdeletions. Almost all mutations detected were newly described except for NR5A1 p.R281C and TEX11 p.M156V. Two missense NR5A1 mutations-p.R281C and p.I244V-were proved to be deleterious by in vitro functional assays. Mutations in TEX11, TEX14, and NR5A1 genes are recurrent causes of NOA, but each gene explains only a very small percentage (less than 4/668; 0.6%). Only the patient with NR5A1 mutations produced viable spermatozoa through micro-TESE, but other patients with TEX11 and TEX14 had poor micro-TESE prognoses.
Conclusions:
A targeted NGS panel is a feasible diagnostic method for patients with NOA. Because each gene implicated explains only a small proportion of such cases, more genes should be included to further increase the diagnostic rate. Considering previous reports, we suggest that only a few genes that are directly linked to meiosis can indicate poor micro-TESE prognosis, such as TEX11, TEX14, and SYCE1.
