{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:50:13Z","timestamp":1786978213912,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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 & Gen Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n This study aims to present novel compound heterozygous\n PROC<\/jats:italic>\n gene variants in a fetus. These variants cause protein C deficiency\u2010associated thrombophilia and are accompanied by prenatal ocular anomalies in the affected fetus.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A fetus presenting with prenatal ocular ultrasound anomalies was enrolled for genetic prenatal diagnosis. Trio whole\u2010exome sequencing (WES) was performed on the fetus and parental samples to explore the genetic etiology. Sanger sequencing was subsequently applied to verify the identified genetic variants.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n WES result revealed two likely pathogenic compound heterozygous variants NM_000312.4: c.[378G>A(p.W126*)]; [658C>T(p.R220W)] in\n PROC<\/jats:italic>\n gene in the fetus, which were inherited from the parents, respectively. Notably, a likely pathogenic homozygous variant of NM_176824.3:c.728G>A(p.C243Y) in\n BBS7<\/jats:italic>\n gene, and a heterozygous variant of NM_012193.4:c.112G>A(p.G38R) in\n FZD4<\/jats:italic>\n gene, as well as a pathogenic heterozygous variant of NM_000435.3:c.1630C>T(p.R544C) in\n NOTCH3<\/jats:italic>\n gene were observed in the mother, which may explain her clinical abnormalities. The maternal\n BBS7<\/jats:italic>\n variant was transmitted to the fetus, whereas the\n FZD4<\/jats:italic>\n and\n NOTCH3<\/jats:italic>\n variants were not detected in the proband. The father exhibited a clinical phenotype of cleft lip and palate, but no corresponding pathogenic genetic variants were identified.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study first reports two rare compound heterozygous\n PROC<\/jats:italic>\n variants in a Chinese fetus, which expands the\u00a0mutational spectrum of protein C deficiency\u2010related thrombophilia in the Chinese population. Furthermore, our findings\u00a0highlight the robust clinical application value of trio\u2010WES in the etiological diagnosis of complex prenatal genetic disorders.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70265","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:52:43Z","timestamp":1784782363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prenatal Etiology Diagnosis of Rare Compound Heterozygous\n \n PROC<\/i>\n <\/scp>\n Gene Variants in a Fetus With Ocular Ultrasonic Anomaly Using Whole Exome Sequencing"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-205X","authenticated-orcid":false,"given":"Jianlong","family":"Zhuang","sequence":"first","affiliation":[{"name":"Prenatal Diagnosis Center Women's and Children's Affiliated Hospital of Huaqiao University, Quanzhou Women's and Children's Hospital Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Huang","sequence":"additional","affiliation":[{"name":"The Teaching and Research Office of Clinical Laboratory Medicine Quanzhou Medical College Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics Berry Genomics Corporation Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8542-5491","authenticated-orcid":false,"given":"Wanyu","family":"Fu","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis Center Women's and Children's Affiliated Hospital of Huaqiao University, Quanzhou Women's and Children's Hospital Quanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000450571"},{"issue":"2","key":"e_1_2_12_3_1","first-page":"73","article-title":"L'image du mois. 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