{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:04:40Z","timestamp":1780405480763,"version":"3.54.1"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471650"],"award-info":[{"award-number":["82471650"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acephalic spermatozoa syndrome (ASS) is a severe form of male infertility, but its genetic etiology remains largely unclear. In this study, we identified a novel homozygous frameshift variant in\n                    <jats:italic>NME5<\/jats:italic>\n                    (c.163delA, p.Ser55Valfs*16) in an infertile man with ASS. Subsequent functional analyses revealed complete loss of NME5 protein. Moreover, ultrastructural analysis of sperm revealed abnormalities in the head\u2010tail coupling apparatus (HTCA) and mitochondrial sheath, as well as defects in the radial spokes and microtubules. Immunofluorescence analysis further confirmed the near absence of the HTCA marker SPATA6 in the patient's sperm. In addition, NME5 expression was assessed across spermatogenic stages in both humans and mice, with predominant expression from round to elongated spermatids. Notably, the patient harboring the\n                    <jats:italic>NME5<\/jats:italic>\n                    variant achieved a favorable clinical outcome after intracytoplasmic sperm injection. Overall, our findings revealed for the first time that\n                    <jats:italic>NME5<\/jats:italic>\n                    is a causative gene for human ASS, further expanding the gene mutational spectrum associated with human male infertility and ultimately offering potential new avenues for diagnostic and therapeutic strategies in clinical practice.\n                  <\/jats:p>","DOI":"10.1111\/cge.70049","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T03:04:05Z","timestamp":1755486245000},"page":"368-373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discovery of a Pathogenic\n                    <scp>\n                      <i>NME5<\/i>\n                    <\/scp>\n                    Variant Underlying Acephalic Spermatozoa Syndrome: Unraveling a Novel Genotype\u2013Phenotype Association in Male Infertility"],"prefix":"10.1111","volume":"109","author":[{"given":"Yunchuan","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingteng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanjuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"West China Institutes of Women and Children's Health, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Reproduction Medical Center of West China Second University Hospital, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education Sichuan University  Chengdu China"},{"name":"Tianfu Jincheng Laboratory, City of Future Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8930-6801","authenticated-orcid":false,"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics\/Gynecology, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiechao","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of 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