{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T12:15:31Z","timestamp":1784117731641,"version":"3.55.0"},"reference-count":68,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary ovarian insufficiency (POI) is a highly heterogeneous condition characterized by the cessation of ovarian function before age 40. While genetic factors play a substantial role, the contribution of structural variants remains incompletely mapped. We conducted a systematic review and in silico genomic re-analysis of published copy number variations (CNVs) in individuals with POI. Following PRISMA guidelines, we aggregated 382 CNVs from 25 studies, standardized genomic coordinates, and filtered variants against population databases. Pathogenicity was reevaluated using ACMG\/ClinGen guidelines, yielding 42 pathogenic\/likely pathogenic variants and 25 large CNVs (&amp;gt;3.5 Mb). Consistent with previous findings, the X chromosome exhibited the highest CNV burden, emphasizing its central role in structural genomic instability and POI pathogenesis. Beyond canonical POI-associated genes, gene ontology and GTEx expression profiling identified several biologically plausible, highly ovary-expressed candidate genes within disrupted loci\u2014notably ATF3, GAS5, PPP4R1, and PRKAA1. Despite their established roles in cellular stress responses, DNA repair, and meiotic progression, these genes remain absent from most commercial POI diagnostic panels. This comprehensive re-analysis highlights the complex structural genomic landscape of POI and suggests that expanding current clinical testing panels to include these under-recognized genes could improve diagnostic yields for genetically unexplained cases.<\/jats:p>","DOI":"10.1210\/clinem\/dgag202","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:35:53Z","timestamp":1778585753000},"page":"2166-2179","source":"Crossref","is-referenced-by-count":1,"title":["Systematic mapping and in silico reevaluation of genomic copy number variations in primary ovarian insufficiency"],"prefix":"10.1210","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6038-2349","authenticated-orcid":false,"given":"Melika","family":"Hossein Garakani","sequence":"first","affiliation":[{"name":"Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR , Tehran 1665659911 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8153-1767","authenticated-orcid":false,"given":"Kianoush","family":"Kakavand","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology of Germ Cells, Institute of Animal Physiology and Genetics, Czech Academy of Sciences , Libechov 277 21 ,","place":["Czech Republic"]},{"name":"Department of Cell Biology, Faculty of Science, Charles University , Prague 128 44 ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1044-0782","authenticated-orcid":false,"given":"Yasaman","family":"Hajiesmaeili","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University , London, ON N6G 2M1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaveh","family":"Haratian","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University , London, ON N6A 5C1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahtab","family":"Z. Moradi","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department, Iranian Hospital , Dubai 333 406 ,","place":["United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2259-0067","authenticated-orcid":false,"given":"Shabnam","family":"Zarei Moradi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR , Tehran 1665659911 ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9049-8057","authenticated-orcid":false,"given":"Anahita","family":"Mohseni Meybodi","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics Division, London Health Sciences Centre, Department of Pathology and Laboratory Medicine (PaLM), Schulich School of Medicine & Dentistry, Western University , London, ON N6A 5C1 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