{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:30:28Z","timestamp":1792431028171,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>HENMT1 encodes a small RNA methyltransferase that plays a crucial role in mouse spermatogenesis through the methylation of the 3\u2032 end of PIWI\u2010interacting RNAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Our study aims to elucidate the relationship between <jats:italic>HENMT1<\/jats:italic> and male infertility in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A consanguineous family, having a single non\u2010obstructive azoospermia patient was recruited for pathogenic variants screening. The research includes genetic analysis and experimental validation using mouse models. The patient was diagnosed with non\u2010obstructive azoospermia. Whole\u2010exome sequencing and subsequent bioinformatic analyses were performed to screen for candidate pathogenic variants. The pathogenicity of the identified variant was assessed and studied in vivo using a mouse model that mimicked the patient's mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Through whole\u2010exome sequencing, we identified a homozygous nonsense variant (c.555G\u00a0&gt;\u00a0A, p.Trp185*) in <jats:italic>HENMT1<\/jats:italic> in the patient. The presence of the mutant <jats:italic>HENMT1<\/jats:italic> mRNA was detected in the patient's blood, and the truncated HENMT1 protein was observed in transfected HEK293T cells. The mutant mice modeling this <jats:italic>HENMT1<\/jats:italic> variant displayed an infertile phenotype similar to that of the patient, characterized by spermiogenesis arrest. Further analysis revealed a significant derepression of retrotransposon LINE1 in the testes of the <jats:italic>Henmt1<\/jats:italic> mutant mice, and increased apoptosis of spermatids.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>Our findings provide the evidence of pathogenicity of the identified <jats:italic>HENMT1<\/jats:italic> variant, thus shedding light on the indispensable role of HENMT1 in human spermatogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13767","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T10:51:09Z","timestamp":1727261469000},"page":"1439-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A homozygous nonsense variant in <i>HENMT1<\/i> causes male infertility in humans and 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