Whole-exome sequencing reveals a novel mutation in the SUN5 gene causing acephalic spermatozoa syndrome

Context Acephalic spermatozoa syndrome (ASS) is one of the most severe male spermatogenic disorders, featuring a large number of headless spermatozoa in the ejaculate. Although genetic factors play an important role in spermatogenesis, only a few genes are correlated with sperm defects and male infertility. Studies have revealed that genetic mutations are the main causes of ASS. Therefore, finding new genes that lead to ASS is significant in choosing the correct treatment methods and genetic counseling for these patients.p Aims This study aimed to identify the genetic causes of ASS in two infertile brothers whose parents are first cousins. Methods Whole-exome sequencing (WES) was performed using peripheral blood genomic DNA. PCR reactions, Sanger sequencing, and immunocytochemistry were performed to confirm the results of WES. Key results We identified a novel homozygous mutation in the SUN5 gene (NM_080675: exon11: c.879dupc: p.k), and Sanger sequencing confirmed our finding. There was no signal of SUN5-antibody in the protein assessment of the spermatozoa from our patient. We conducted two intracytoplasmic sperm injections (ICSI) cycles for the proband, however, the treatment did not result in his partner achieving pregnancy. Conclusions Our findings suggest that the novel mutation of the SUN5 gene is responsible for ASS. Implications These results highlight the diagnostic value of identifying SUN5 mutations in in patients with ASS. The current findings contribute to a better understanding of the genetic basis of ASS and can inform future clinical decisions as more data become available.