فهرست نشریات علمی دسترسی آزاد ایران

Background: Infertility affects approximately 50 million couples worldwide, with both men and women being equallyaffected. Male infertility is a complex issue with genetic factors playing a significant role. Conditions such asKlinefelter syndrome (XXY), Y chromosome microdeletions (YCMDs), and monogenic mutations can contribute tomale infertility. Currently, hereditary factors account for 4% of male infertility cases, while the causes of 60-70% ofcases remain unknown. Ongoing research aims to identify new genes and variants related to male fertility to improvediagnostic methods. More than 2000 genes are believed to be involved in preserving germ cells and ensuring normalmeiosis, with more than 100 genes already identified for male infertility.Materials and Methods: In this case series study, we assessed a patient with unexplained male infertility, who alsohad a brother with a similar issue. We used whole exome sequencing (WES) technology, segregation analysis andanalyzed the data through bioinformatics tools.Results: Bioinformatics analysis and Sanger sequencing revealed that two infertile brothers had a compound heterozygous(CH) mutation with missense variants in dynein axonemal heavy chain 5 (DNAH5) gene: one variant in exon9, (c.1121T>C: p.Ile374Thr), and another in exon 66, (c.11437C>T: p.Arg3813Trp). The protein structure analysisshowed that the Ile374Thr variant is located near the outer dynein arm-docking subunit 1 (ODA-D1) and ODA-D3.Additionally, the Arg3813Trp variant replaces the positively charged arginine with a hydrophobic tryptophan residue,which may lead to local instability in the protein structure, particularly in the ATP-binding site.Conclusion: Our study reports a CH presence of a missense variant in DNAH5 within a family experiencing maleinfertility. In silico structural predictions suggest a potential role of these DNAH5 variants in causing fertility issues.