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Whole\u2010exome sequencing was performed on the patients to identify pathogenic mutations for infertility. Western blotting and immunofluorescence analysis detected the expression level and localization of CEP250. Co\u2010immunoprecipitation detected the protein\u2010protein interactions. <jats:italic>Cep250\u2010KI<\/jats:italic> mice were generated by the CRISPR\u2010Cas9 system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, 10 patients diagnosed with acephalic spermatozoa syndrome were recruited, and a homozygous loss\u2010of\u2010function mutation in <jats:italic>CEP250<\/jats:italic> (NM_007186: c. 4710_4723del: p. E1570fs*39) was identified from a consanguineous Han Chinese family. Immunofluorescence experiments revealed a decreased CEP250 signal in the neck region of the patient's sperm compared with the normal. Co\u2010immunoprecipitation results indicated reduced interaction between SUN5\/PMFBP1 and mutant CEP250 compared with the wild\u2010type, possibly due to the absence of complete 2272\u20132442 amino acids. Besides, the patient can be effectively treated with intracytoplasmic sperm injections. Nevertheless, <jats:italic>Cep250\u2010KI<\/jats:italic> male mice exhibit non\u2010obstructive azoospermia, which indicates the different functions in CEP250 between human and mouse spermatogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, <jats:italic>CEP250<\/jats:italic> may represent a novel pathogenic gene for acephalic spermatozoa syndrome in humans, and we provide precise genetic diagnosis and treatment strategies for the patient.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13827","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T06:24:37Z","timestamp":1735280677000},"page":"1285-1291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A homozygous loss\u2010of\u2010function mutation in <i>CEP250<\/i> is associated with acephalic spermatozoa syndrome in 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