{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:00:06Z","timestamp":1790830806797,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":272,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background\/Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>DICER1<\/jats:italic>\n                      \u2010related tumor predisposition is a rare hereditary tumor predisposition disorder characterized by autosomal dominant inheritance, reduced penetrance, and variable expressivity. This study is aimed at describing the clinical and molecular spectrum of\n                      <jats:italic>DICER1<\/jats:italic>\n                      \u2010related tumor predisposition in an Argentine pediatric cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Methods<\/jats:title>\n                    <jats:p>\n                      Seventeen unrelated patients with\n                      <jats:italic>DICER1<\/jats:italic>\n                      \u2010related tumor predisposition and 54 relatives were evaluated at \u201cProf. Dr. J. P. Garrahan\u201d Pediatric Hospital (Buenos Aires, Argentina) between 2014 and 2024. Germline and somatic\n                      <jats:italic>DICER1<\/jats:italic>\n                      variants were analyzed using Sanger or next\u2010generation sequencing. Functional assays were performed for selected intronic variants. Three samples of poorly differentiated thyroid carcinoma were also included.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixteen distinct germline variants were identified in the 17 index cases, including 12 novel alterations (75%). One quarter of the variants were de novo. Thyroid involvement, particularly multinodular goiter and papillary thyroid carcinoma, was the most common presentation and frequently coexisted with ovarian Sertoli\u2013Leydig cell tumors or embryonal rhabdomyosarcoma. Two novel intronic variants were confirmed to affect splicing by RT\u2010PCR. Somatic \u201chotspot\u201d mutations in exons 24\u201325 (RNase IIIb domain) were detected in most tumors, consistent with the two\u2010hit model. The identification of asymptomatic carriers enabled early surveillance and preventive interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study expands the molecular spectrum of germline\n                      <jats:italic>DICER1<\/jats:italic>\n                      variants, reinforces the predominance of thyroid involvement, and highlights the value of molecular testing for diagnosis, genetic counseling, and early intervention. Ethical considerations regarding surveillance and management of asymptomatic carriers remain an important area in need of future guidance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/3621830","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:45:09Z","timestamp":1790829909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanding the Molecular Data of\n                    <i>DICER1<\/i>\n                    \u2010Related Tumor Predisposition: Novel Germline Variants in an Argentine Pediatric Cohort"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6061-3208","authenticated-orcid":false,"given":"Sof\u00eda","family":"Trobo","sequence":"first","affiliation":[{"name":"Endocrinology Molecular Laboratory Hospital de Pediatr\u00eda Prof. Dr. Juan P. 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