{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:49:46Z","timestamp":1783982986321,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"the Russian Science Foundation","doi-asserted-by":"publisher","award":["25-25-00577"],"award-info":[{"award-number":["25-25-00577"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: 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. Methods: The patient underwent clinical, andrological, and genetic examinations, including semen analysis, transmission electron microscopy, cytogenetic examination, molecular analysis of the AZF locus and the CFTR gene, whole-exome sequencing, and Sanger sequencing. Results: 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 (\u201cimmature\u201d) chromatin was also observed. No chromosomal abnormalities, Y chromosome microdeletions, or pathogenic CFTR gene variants were identified. Whole-exome sequencing revealed a novel c.821G&gt;C variant (chrX:127185365G&gt;C; NM_138289.4) in the ACTRT1 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 ACTRT1 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. Conclusions: This study suggests a potential link between a novel ACTRT1 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.<\/jats:p>","DOI":"10.3390\/genes16121422","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T09:34:37Z","timestamp":1764581677000},"page":"1422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Variant of the ACTRT1 Gene Is Potentially Associated with Oligoasthenoteratozoospermia, Acrosome Detachment, and Fertilization Failure"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1389-4731","authenticated-orcid":false,"given":"Olga","family":"Solovova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0535-4081","authenticated-orcid":false,"given":"Sabina","family":"Khayat","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1974-5005","authenticated-orcid":false,"given":"Sergey","family":"Bogolyubov","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre, 117292 Moscow, Russia"},{"name":"Next Generation Clinic, 107140 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8422-4962","authenticated-orcid":false,"given":"Elizaveta","family":"Bragina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"},{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-6947","authenticated-orcid":false,"given":"Tatiana","family":"Cherevatova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7615-8512","authenticated-orcid":false,"given":"Vyacheslav","family":"Chernykh","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"},{"name":"Institute of Biomedicine, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.beem.2010.08.006","article-title":"Male Infertility: Pathogenesis and Clinical Diagnosis","volume":"25","author":"Krausz","year":"2011","journal-title":"Best. 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