{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:05:16Z","timestamp":1790168716722,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anophthalmia\/microphthalmia (A\/M) is a severe congenital ocular malformation characterized by the complete absence or small size of the eye bulb. Interpreting copy number variations (CNVs) in A\/M is challenged by variable genotype\u2013phenotype correlations and reduced penetrance. This study investigated the genetic etiology of A\/M\u2010associated CNVs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genomic profiling was performed on four unrelated families presenting with ocular anomalies or harboring A\/M\u2010susceptible CNVs. Variants were evaluated by integrating American College of Medical Genetics and Genomics (ACMG) guidelines with clinical phenotypes and familial segregation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      An inherited 8.13\u2009Mb deletion (8p23.3p23.1) in Patient 1 was excluded due to genotype\u2013phenotype mismatch. Patients 2 and 3 harbored de novo pathogenic deletions involving\n                      <jats:italic>OTX2<\/jats:italic>\n                      (14q22.3) and\n                      <jats:italic>SOX2<\/jats:italic>\n                      (3q26.33), causing typical A\/M. Case 4 revealed a 14q22.2q23.1 deletion encompassing\n                      <jats:italic>OTX2<\/jats:italic>\n                      in a fetus and mother without ocular anomalies, consistent with the incomplete penetrance of\n                      <jats:italic>OTX2<\/jats:italic>\n                      \u2010related microphthalmia. Thus, CNV\u2010induced haploinsufficiency causes A\/M with high phenotypic variability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Accurate CNV interpretation requires robust genotype\u2013phenotype correlation and careful assessment of incomplete penetrance to prevent diagnostic pitfalls and improve genetic counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70282","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:52:28Z","timestamp":1788511948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Profiling of Anophthalmia\/Microphthalmia\u2010Associated\n                    <scp>CNVs<\/scp>\n                    Reveals Complex Genotype\u2013Phenotype Correlations and Incomplete Penetrance"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2121-6807","authenticated-orcid":false,"given":"Dong","family":"Wu","sequence":"first","affiliation":[{"name":"Medical Genetics Institute of Henan Provincial People's Hospital  Zhengzhou China"},{"name":"NHC Key Laboratory of Birth Defects Prevention, Institute of Reproductive Health, Henan Academy of Innovations in Medical Science  Zhengzhou China"},{"name":"Department of Medical Genetics The Affiliated People's Hospital, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute of Henan Provincial People's Hospital  Zhengzhou China"},{"name":"NHC Key Laboratory of Birth Defects Prevention, Institute of Reproductive Health, Henan Academy of Innovations in Medical Science  Zhengzhou China"},{"name":"Department of Medical Genetics The Affiliated People's Hospital, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute of Henan Provincial People's Hospital  Zhengzhou China"},{"name":"NHC Key Laboratory of Birth Defects Prevention, Institute of Reproductive Health, Henan Academy of Innovations in Medical Science  Zhengzhou China"},{"name":"Department of Medical Genetics The Affiliated People's Hospital, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute of Henan Provincial People's Hospital  Zhengzhou China"},{"name":"NHC Key Laboratory of Birth Defects Prevention, Institute of Reproductive Health, Henan Academy of Innovations in Medical Science  Zhengzhou China"},{"name":"Department of Medical Genetics The Affiliated People's Hospital, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1024-9398","authenticated-orcid":false,"given":"Qiaofang","family":"Hou","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute of Henan Provincial People's Hospital  Zhengzhou China"},{"name":"Department of Medical Genetics The Affiliated People's Hospital, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute of Henan Provincial People's Hospital  Zhengzhou China"},{"name":"Department of Medical Genetics The Affiliated People's Hospital, Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixiu","family":"Liao","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute of Henan Provincial People's Hospital  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