A Novel Variant of the ACTRT1 Gene Is Potentially Associated with Oligoasthenoteratozoospermia, Acrosome Detachment, and Fertilization Failure

<b>Background:</b> Male infertility is a common reproductive disorder, affecting about 7% of men in the general population. Despite its prevalence, the cause of infertility is often unknown. This case report presents the results of a comprehensive evaluation of a patient with severe oligoasthenoteratozoospermia and primary infertility. <b>Methods:</b> The patient underwent clinical, andrological, and genetic examinations, including semen analysis, transmission electron microscopy, cytogenetic examination, molecular analysis of the AZF locus and the <i>CFTR</i> gene, whole-exome sequencing, and Sanger sequencing. <b>Results:</b> Semen analysis revealed severe oligoasthenoteratozoospermia. Transmission electron microscopy showed acrosome detachment from the nucleus in 49% of the spermatozoa. A high percentage (54%) of spermatozoa with insufficiently condensed ("immature") chromatin was also observed. No chromosomal abnormalities, Y chromosome microdeletions, or pathogenic <i>CFTR</i> gene variants were identified. Whole-exome sequencing revealed a novel c.821G>C variant (chrX:127185365G>C; NM_138289.4) in the <i>ACTRT1</i> gene (Xq25). This variant was hemizygous in the patient and heterozygous in his mother, as determined by Sanger sequencing. According to the ACMG guidelines (PM2, PP3), this missense variant in the <i>ACTRT1</i> gene was classified as a variant of uncertain clinical significance (VUS). Amino acid conservation and 3D protein modeling predict that the identified variant has a deleterious effect on the protein. <b>Conclusions:</b> This study suggests a potential link between a novel <i>ACTRT1</i> variant and a specific teratozoospermia phenotype. Further functional studies are needed to confirm this association and determine the role of the gene in X-linked male infertility.