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In this study, we performed whole\u2010exome sequencing on 303 independent females with EEA and identified 16 patients with biallelic pathogenic variants in SCMC genes (<jats:italic>NLRP2<\/jats:italic>, <jats:italic>NLRP5<\/jats:italic>, <jats:italic>PADI6<\/jats:italic>, and <jats:italic>TLE6<\/jats:italic>), accounting for 5.3% of EEA cases. <jats:italic>NLRP5<\/jats:italic> had the highest prevalence, with 7 out of 16 cases (43.8%). A total of 23 novel variants were identified, including 13 missense, eight loss\u2010of\u2010function, one in\u2010frame insertion, and one large 6.9\u2009kb deletion. Functional predictions using mCSM indicated that nine missense variants destabilize SCMC structure. Additionally, RT\u2010PCR and cDNA sequencing demonstrated that the synonymous variant in <jats:italic>TLE6<\/jats:italic> (c.180G&gt;A) impacts splicing and induces nonsense\u2010mediated decay. Taken together, our findings revealed that novel biallelic variants in SCMC genes were associated with human EEA, which expands the spectrum of genetic causes and facilitates the genetic diagnosis of female infertility with EEA.<\/jats:p>","DOI":"10.1111\/cge.14696","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T07:31:15Z","timestamp":1738222275000},"page":"680-687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Novel <scp>SCMC<\/scp> Gene Variants Associated With Early Embryonic Arrest"],"prefix":"10.1111","volume":"107","author":[{"given":"Changlong","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health Shandong University  Jinan Shandong China"},{"name":"National Research Center for Assisted Reproductive Technology and Reproductive Genetics Shandong University  Jinan Shandong China"},{"name":"Key Laboratory of Reproductive Endocrinology (Shandong University) Ministry of Education  Jinan Shandong China"},{"name":"Shandong Technology Innovation Center for Reproductive Health  Jinan Shandong China"},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health  Jinan Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health Shandong University  Jinan Shandong China"},{"name":"National Research Center for Assisted Reproductive Technology and Reproductive Genetics Shandong University  Jinan Shandong China"},{"name":"Key Laboratory of Reproductive Endocrinology (Shandong University) Ministry of Education  Jinan Shandong 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