{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:03:00Z","timestamp":1780473780487,"version":"3.54.1"},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF2020R1F1A1076705"],"award-info":[{"award-number":["NRF2020R1F1A1076705"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS\u20102022\u2010II220333"],"award-info":[{"award-number":["RS\u20102022\u2010II220333"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["IITP\u20102026\u2010RS\u20102024\u201000438263"],"award-info":[{"award-number":["IITP\u20102026\u2010RS\u20102024\u201000438263"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018688","name":"Korea Disease Control and Prevention Agency","doi-asserted-by":"publisher","award":["CODA_S2400008\u201001"],"award-info":[{"award-number":["CODA_S2400008\u201001"]}],"id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neurodevelopmental disorders (NDDs) often remain unexplained due to limited assessment of non\u2010coding genomic elements. Motivated by recent reports implicating\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    , which encodes a spliceosomal small nuclear RNA (snRNA), we analyzed whole\u2010genome sequencing data from 15\u2009450 Korean individuals, including 2797 unrelated NDD probands. Rare pathogenic\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    variants were identified in 20 probands (0.72%), including 17 (85%) with a recurrent n.64_65insT variant. RNA secondary structure modeling and molecular dynamics simulations demonstrated that n.64_65insT disrupts the U4\/U6 snRNA duplex and impairs exposure of the U6 ACAGAGA motif required for 5\u2032 splice\u2010site recognition. Whole\u2010blood RNA\u2010seq from carriers revealed increased alternative 5\u2032 splice\u2010site usage and dysregulation of immune, chromosomal, and DNA metabolic gene programs. Clinically, affected individuals presented with global developmental delay, microcephaly, seizures, failure to thrive, and dysmorphic features. These findings establish\n                    <jats:italic>RNU4\u20102<\/jats:italic>\n                    , particularly n.64_65insT, as a cause of early\u2010onset NDD. We advocate for routine assessment of spliceosomal RNA genes in genomic diagnostics and reanalysis of unsolved cases to improve yield and guide counseling in rare neurodevelopmental syndromes.\n                  <\/jats:p>","DOI":"10.1111\/cge.70154","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:55:58Z","timestamp":1772970958000},"page":"90-95","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Impact of\n                    <i>RNU4\u20102<\/i>\n                    Defects on Neurodevelopmental Disorders in a Korean Population"],"prefix":"10.1111","volume":"110","author":[{"given":"Juhyeon","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Korea University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungbok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Seoul National University Hospital  Seoul Korea"},{"name":"Department of Pediatrics Seoul National University College of Medicine, Seoul National University Children's Hospital  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Seoul National University Hospital  Seoul Korea"},{"name":"Department of Pediatrics Seoul National University College of Medicine, Seoul National University Children's Hospital  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taekeun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Korea University College of Medicine  Seoul 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