Establishment and clinical significance of genetic factor screening method for patients with nonobstructive azoospermia based on whole exon sequencing technology.

Abstract

Background: Non-obstructive azoospermia (NOA) is a severe form of male infertility, affecting 10-20% of azoospermic men. Although some NOA genes have been identified, the genetic causes of spermatogenesis failure in NOA remain unclear. This study aimed to identify and characterize genes and mutations associated with NOA.

Methods: Thirty NOA patients were selected for whole-exome sequencing (WES). Patients with chromosomal abnormalities, chromosome copy number issues, or Y chromosome microdeletions were excluded. Relevant genes and mutations in NOA patients were comprehensively screened using WES, MutationTaster software, and related databases. Sequencing results were analyzed for allele screening, mutation deleteriousness, and mutation site prediction to identify potential NOA-associated genes. The study also predicted altered gene function due to mutations and assessed pathogenicity from DNA sequence alterations.

Results: The study screened 37 genes with 56 variant loci, identifying 27 genes with 34 variant loci related to NOA, including CFAP65, SEPTIN12, ZMYND15, DNAH2, CEP112, SHOC1, DNAH10, ACTL9, CFAP43, DNAH17, DNAH1, ARMC2, AK7, PMFBP1, FSIP2, SPATA16, TSGA10, SPEF2, CFAP69, TTC21A, NDNF, ADCY10, GATA4, CYP17A1, CHD7, CHD7, SEMA3A, and CFTR. Notable findings included the variant c.1223C>A p.S408* in the CFAP65 gene and potential associations of genes such as CFAP43, CFAP69, ZMYND15, DNAH17, and DNAH2 with spermatogenic disorders.

Conclusions: The study identified genes related to spermatogenic disorders in azoospermia, providing a reference for clinical genetic diagnosis and basic NOA research.