Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Our investigation aimed at the identification of genetic mutations responsible for teratozoospermic infertility in three infertile male patients (P1, P2, and P3), each exhibiting distinct morphological defects in spermatozoa. P1 exhibited a special case of sperm heads in coiled tails (HIC), elongated heads, and various tail defects. Other patients (P2 and P3) showed various head and tail morphological deformities. We employed whole exome sequencing (WES) to investigate the genetic basis of male infertility associated with sperm morphological defects. Filtering of the exome sequencing data involved criteria such as minor allele frequency (MAF) <0.003, ALFA project frequency<0.001, 1000 Genomes frequency <0.003, Grantham score >40, PolyPhen-2 score >0.70, SIFT score <0.05, and PhyloP score ≥0. Variants meeting these criteria were cross-referenced with an in-house dataset of 29 exomes of fertile control males, focusing on those affecting conserved amino acid residues, causing insertions/deletions, and resulting in protein truncation with a Combined Annotation Dependent Depletion (CADD) score ≥10. The prioritization of variants was based on their potential roles in spermiogenesis and their possible role in the causation of respective morphological deformities. The potential mutations were assessed through various in-silico analysis tools to further evaluate their pathogenicity. Our investigation identified a heterozygous mutation (c.826C>T) in the SPEM1 gene in P1, a heterozygous mutation (c.5026G>A) in the DNAH17 gene in P2, and a heterozygous mutation (c.4511A>G) in the SPAG17 gene in P3, as potential pathogenic variants that led to teratozoospermic infertility in the cases under investigation. We reported the first human mutation in the SPEM1 gene as a cause of coiled sperm tails, alongside other documented cases. These findings offer insights into the genetic causes underlying human male infertility associated with sperm morphological anomalies.