{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T09:31:05Z","timestamp":1769247065639,"version":"3.49.0"},"reference-count":18,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402160"],"award-info":[{"award-number":["82402160"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471687"],"award-info":[{"award-number":["82471687"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["22Y11906700"],"award-info":[{"award-number":["22Y11906700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Fetal central nervous system (CNS) anomalies are among the most common congenital malformations, yet the overall prenatal diagnostic yield of current genetic testing remains below 40%. Variants in\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    , a non\u2010coding gene encoding the U4 small nuclear RNA (snRNA), have recently been linked to a novel highly recurrent dominant neurodevelopmental disorder termed ReNU syndrome. While its postnatal phenotype has been well characterized, the contribution of\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    to fetal CNS anomalies remains unexplored. In this study, we retrospectively analyzed 148 fetuses with CNS anomalies who had non\u2010diagnostic results from karyotyping, chromosomal microarray analysis, and exome sequencing. Targeted Sanger sequencing of\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    was performed to identify pathogenic variants. Two fetuses harbored the same de novo recurrent variant, n.64_65insT, corresponding to a diagnostic yield of 1.35%. Both cases presented with microcephaly, suggesting that it is a key prenatal feature of ReNU syndrome. Furthermore, molecular confirmation of\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    resolved a decade\u2010long diagnostic odyssey in one family by excluding an inherited Xp22.13 duplication of uncertain significance as the causal variant. In conclusion, this study provides the first systematic prenatal evaluation of\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    in fetuses with CNS anomalies, thereby expanding the prenatal phenotypic spectrum of ReNU syndrome. Incorporating\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    testing into prenatal genetic workflows may enhance diagnostic yield, enable precise genetic counseling, and support informed reproductive decision\u2010making.\n                  <\/jats:p>","DOI":"10.1002\/ajmgc.70002","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T06:46:47Z","timestamp":1766731607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal Evaluation of\n                    <i>RNU4\u20102<\/i>\n                    Variants in Fetuses With Central Nervous System Anomalies"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8966-7890","authenticated-orcid":false,"given":"Yiyao","family":"Chen","sequence":"first","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Han","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunyun","family":"Cao","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanlan","family":"Zhang","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-8807","authenticated-orcid":false,"given":"Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinrong","family":"Zhao","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjing","family":"Hu","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai China"},{"name":"Institute of Birth Defects and Rare Diseases, School of Medicine, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4271-4295","authenticated-orcid":false,"given":"Ruiyu","family":"Ma","sequence":"additional","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai China"},{"name":"Institute of Birth Defects and Rare Diseases, 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