{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:40:16Z","timestamp":1784302816477,"version":"3.55.0"},"reference-count":18,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R368\u20102021\u2010428"],"award-info":[{"award-number":["R368\u20102021\u2010428"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["2019\u20105934"],"award-info":[{"award-number":["2019\u20105934"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["2019\u20105996"],"award-info":[{"award-number":["2019\u20105996"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["2023\u201000106"],"award-info":[{"award-number":["2023\u201000106"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pathogenic germline variants in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>DICER1<\/jats:italic>\n                    <\/jats:styled-content>\n                    predispose to pleuropulmonary blastoma, multinodular goitre, embryonal rhabdomyosarcomas of the uterine cervix, ovarian Sertoli\u2010Leydig cell tumour and a broader spectrum of pathologies. Here, we report a 35\u2010year\u2010old female with diagnoses of pineoblastoma, embryonal rhabdomyosarcoma, leiomyosarcoma, two meningiomas, and a germline\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>DICER1<\/jats:italic>\n                    <\/jats:styled-content>\n                    c.4206+\n                    <jats:styled-content style=\"fixed-case\">1G<\/jats:styled-content>\n                    &gt;C, p.(?) variant. The variant was classified as a variant of unknown significance (\n                    <jats:styled-content style=\"fixed-case\">VUS<\/jats:styled-content>\n                    ) based on the current\n                    <jats:styled-content style=\"fixed-case\">ACMG<\/jats:styled-content>\n                    \/\n                    <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\n                    gene\u2010specific\n                    <jats:styled-content style=\"fixed-case\">DICER1<\/jats:styled-content>\n                    guidelines. Additional functional analysis showed that the variant clearly abrogates the function of\n                    <jats:styled-content style=\"fixed-case\">DICER1<\/jats:styled-content>\n                    and therefore PS3_Supporting evidence is included in the classification. Based on this the variant is reclassified as likely pathogenic. Moreover, our data suggest that the current\n                    <jats:styled-content style=\"fixed-case\">ACMG<\/jats:styled-content>\n                    \/\n                    <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\n                    gene\u2010specific\n                    <jats:styled-content style=\"fixed-case\">DICER1<\/jats:styled-content>\n                    guidelines should be modified in relation to the level of evidence strength (moderate to strong\/very strong) for exon 22 skipping as well as to the use of the functional evidence (\n                    <jats:styled-content style=\"fixed-case\">PS3<\/jats:styled-content>\n                    ) code.\n                  <\/jats:p>","DOI":"10.1111\/cge.70110","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:59:49Z","timestamp":1763978389000},"page":"931-936","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional Analysis and Clinical Data Reclassify the\n                    <scp>\n                      <i>DICER1<\/i>\n                    <\/scp>\n                    c.4206+\n                    <scp>1G<\/scp>\n                    &gt;C Variant, Leading to Exon 22 Skipping, as Likely Pathogenic"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0842-1729","authenticated-orcid":false,"given":"Sebastian","family":"Walpole","sequence":"first","affiliation":[{"name":"School of Medicine University of Queensland  Brisbane Australia"},{"name":"Department of Clinical Genetics University Hospital of Copenhagen  Copenhagen Denmark"},{"name":"Princess Alexandra Hospital  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1082-018X","authenticated-orcid":false,"given":"Miren Itxaso","family":"Santiago\u2010Vela","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Birkedal","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University Hospital of Copenhagen  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyi","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier Bofill\u2010De","family":"Ros","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"van Overeem Hansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University Hospital of Copenhagen  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin A. W.","family":"Wadt","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics University Hospital of Copenhagen  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03049"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174334"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3802"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.083790"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.83"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-018-4040-1"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.6746.1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103428"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.727970"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/9537832"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.06.002"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-023-00336-1"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05723-3"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.11.034"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23877"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.555"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70110","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70110","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:24:14Z","timestamp":1775802254000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":18,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/cge.70110"],"URL":"https:\/\/doi.org\/10.1111\/cge.70110","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,24]]},"assertion":[{"value":"2025-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}