Exome sequencing-based identification of DNAAF1 variants implicated in male infertility and primary ciliary...

Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive disorder caused by impaired cilia and flagella function. Despite advances in molecular diagnostics, pathogenic variants remain to be detected in a subset of clinically diagnosed individuals. In the present case, abdominal ultrasonography revealed situs inversus of the liver and spleen, and chest X-ray demonstrated dextrocardia. Semen analysis showed markedly reduced sperm motility, consistent with ciliary dysfunction, and the patient exhibited additional clinical features characteristic of PCD. Exome sequencing (ES) revealed biallelic variants in dynein axonemal assembly factor 1 (DNAAF1) (NM_178452.6), including a missense variant, c.524T>C (p.Leu175Pro), and a nonsense variant, c.1462C>T (p.Arg488*). Segregation analysis was performed in the available family members and confirmed that each parent carried one of the variants in a heterozygous state. Bioinformatic predictions supported the pathogenic potential of identified variants, suggesting that they likely underlie the ciliary defects observed in the affected individual. Taken together, these findings implicate previously reported DNAAF1 variant c.1462C>T and newly identified variant c.524T>C in PCD associated with male infertility. The predicted structural perturbation in DNAAF1 protein structure is likely to impair dynein arm assembly, leading to loss of ciliary motility and the resultant clinical phenotype.