{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:18:09Z","timestamp":1793395089511,"version":"4.5.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T00:00:00Z","timestamp":1632182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M661521"],"award-info":[{"award-number":["2019M661521"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Testis-expressed gene 11 (<jats:italic>TEX11<\/jats:italic>) mutation has been associated with non-obstructive azoospermia (NOA) and meiotic arrest. An analogous mutation of <jats:italic>TEX11<\/jats:italic> in the mouse impairs meiosis and can be rescued by <jats:italic>in vitro<\/jats:italic> expansion of SSCs and gene therapy. However, a lack of genetic screening of a large cohort of Asian patients (including pedigree analysis) and proper functional evaluation limit the clinical application of <jats:italic>TEX11<\/jats:italic> mutation screening. Thus, we performed whole-exome sequencing (WES) in 479 patients with NOA and identified three novel mutations (two splicing mutations and one missense mutation) in <jats:italic>TEX11<\/jats:italic> in three pairs of siblings from three families and four novel pathogenic mutations (three frameshift mutations and a non-sense mutation) of <jats:italic>TEX11<\/jats:italic> in four sporadic NOA-affected cases. Novel variants among family members were segregated by disease phenotype, and all the seven mutations were predicted to be pathogenic. Histological analysis showed that three patients with <jats:italic>TEX11<\/jats:italic> mutations underwent meiotic arrest. The four mutations that resulted in protein truncations and defective meiosis-specific sporulation domain SPO22 were validated by Western blot. In total, we find seven of 479 patients of NOA (1.5%) carrying <jats:italic>TEX11<\/jats:italic> mutations. Our study expands the knowledge of mutations of <jats:italic>TEX11<\/jats:italic> gene in Asian patients with NOA. The high prevalence and X-linked inherited mode indicated that <jats:italic>TEX11<\/jats:italic> might be included in genetic screening panels for the clinical evaluation of patients with NOA.<\/jats:p>","DOI":"10.3389\/fgene.2021.741355","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T13:06:27Z","timestamp":1632229587000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Novel Hemizygous Mutations of TEX11 Cause Meiotic Arrest and Non-obstructive Azoospermia in Chinese Han Population"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhiyong","family":"Ji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chencheng","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijue","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erlei","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nachuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000042","article-title":"ZIP4H (TEX11) deficiency in the mouse impairs meiotic double strand break repair and the regulation of crossing over.","volume":"4","author":"Adelman","year":"2008","journal-title":"PLoS Genet."},{"key":"B2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male infertility.","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030083","article-title":"Zip4\/Spo22 is required for class I CO formation but not for synapsis completion in Arabidopsis thaliana.","volume":"3","author":"Chelysheva","year":"2007","journal-title":"PLoS Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1093\/humupd\/dmz028","article-title":"Sperm recovery and ICSI outcomes in men with non-obstructive azoospermia: a systematic review and meta-analysis.","volume":"25","author":"Corona","year":"2019","journal-title":"Hum. 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