Targeted next-generation sequencing panel screening of 668 Chinese patients with non-obstructive azoospermia

Area of Science:

• Human Genetics
• Reproductive Medicine
• Molecular Biology

Background:

• Non-obstructive azoospermia (NOA) affects male fertility, with genetic factors playing a significant role.
• Identifying causative genes is crucial for diagnosis and understanding reproductive potential.

Purpose of the Study:

• To determine the molecular diagnosis rate in Chinese men with NOA using targeted next-generation sequencing (NGS) panels.
• To identify recurrent causative genes and assess their prognostic value for microsurgical testicular sperm extraction (micro-TESE).

Main Methods:

• Targeted NGS panel screening of 668 Chinese men diagnosed with NOA.
• Follow-up of micro-TESE outcomes in six patients with pathogenic mutations.
• In vitro functional assays for NR5A1 variants (p.I224V and p.R281C).

Main Results:

• NGS panels explained 2.1% of NOA cases after excluding chromosomal abnormalities and Y deletions.
• Mutations in TEX11, TEX14, and NR5A1 were identified as recurrent causes, each accounting for <0.6% of cases.
• Only patients with NR5A1 mutations yielded viable sperm via micro-TESE; TEX11 and TEX14 mutations correlated with poor micro-TESE prognosis.

Conclusions:

• Targeted NGS panels are effective for diagnosing NOA.
• Expanding gene panels is necessary to increase the diagnostic yield.
• Specific genes, particularly those linked to meiosis (e.g., TEX11, TEX14, SYCE1), may indicate poor micro-TESE outcomes.