{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:26:40Z","timestamp":1783488400949,"version":"3.55.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T00:00:00Z","timestamp":1568332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>DICER1 syndrome is an autosomal dominant disorder that predisposes individuals to develop benign or malignant tumours from infancy to adulthood. There is low\u2010to\u2010moderate penetrance of tumour development, which is sex\u2010 and age\u2010dependent. Multinodular goitre (MNG) is among the most highly penetrant phenotype of the disorder, especially in females.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>We report a series of eight families referred for childhood\u2010onset of MNG or DICER1\u2010related tumours with familial history of MNG in relatives. No additional families with these criteria stated were identified during the same date. We screened DNA samples from the probands and members of their family (40) for constitutional <jats:italic>DICER1<\/jats:italic> variants using Next Generation Sequencing tools.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Germline pathogenic <jats:italic>DICER1<\/jats:italic> gene variants were identified in all probands and several of their relatives: 64% presented with MNG\/thyroidectomy as the phenotypic expression of the syndrome. <jats:italic>DICER1<\/jats:italic> gene variants were identified in the RNAseIII and the PAZ domains. All tumour tissues studied presented clonal pathogenic variants in hotspot regions. Early identification of <jats:italic>DICER1<\/jats:italic> variant carriers has permitted diagnosis and therapeutic scheme correction for two patients and cascade testing in relatives.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Multinodular goitre is uncommon in children. Childhood\u2010onset MNG, multiple occurrences of the disease within the same family, or its association with rare benign or malignant tumours should raise suspicions of anomalies in the <jats:italic>DICER1<\/jats:italic> gene, as proposed by recent international recommendations. Early detection of <jats:italic>DICER1<\/jats:italic> pathogenic variants has important consequences in terms of therapeutic strategy, early tumour screening, and genetic counselling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14074","type":"journal-article","created":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T14:38:57Z","timestamp":1565707137000},"page":"669-675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Multinodular goitre is a gateway for molecular testing of DICER1 syndrome"],"prefix":"10.1111","volume":"91","author":[{"given":"Isabelle","family":"Oliver\u2010Petit","sequence":"first","affiliation":[{"name":"Endocrine, Genetics, Bone Diseases, and Pediatric Gynecology unit Children's Hospital, CHU Toulouse Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Isabelle","family":"Bertozzi","sequence":"additional","affiliation":[{"name":"Hematology and Oncology 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