{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:26:06Z","timestamp":1790886366954,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Familial multinodular goiter (MNG), with or without ovarian Sertoli-Leydig cell tumor (SLCT), has been linked to DICER1 syndrome. We aimed to search for the presence of a germline<jats:italic>DICER1<\/jats:italic>mutation in a large family with a remarkable history of MNG and SLCT, and to further explore the relevance of the identified mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and methods<\/jats:title><jats:p>Sanger sequencing, Fluidigm Access Array and multiplex ligation-dependent probe amplification (MLPA) techniques were used to screen for<jats:italic>DICER1<\/jats:italic>mutations in germline DNA from 16 family members. Where available, tumor DNA was also studied. mRNA and protein extracted from carriers\u2019 lymphocytes were used to characterize the expression of the mutant DICER1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nine of 16 tested individuals carried a germline, in-frame<jats:italic>DICER1<\/jats:italic>deletion (c.4207-41_5364+1034del), which resulted in the loss of exons 23 and 24 from the cDNA. The mutant transcript does not undergo nonsense-mediated decay and the protein is devoid of specific metal ion-binding amino acids (p.E1705 and p.D1709) in the RNase IIIb domain. In addition, characteristic somatic \u2018second hit\u2019 mutations in this region were found on the other allele in tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patients with DICER1 syndrome usually present a combination of a typically truncating germline<jats:italic>DICER1<\/jats:italic>mutation and a tumor-specific hotspot missense mutation within the sequence encoding the RNase IIIb domain. The in-frame deletion found in this family suggests that the germline absence of p.E1705 and p.D1709, which are crucial for RNase IIIb activity, may be enough to permit DICER1 syndrome to occur.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-17-0904","type":"journal-article","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T01:57:42Z","timestamp":1512007062000},"page":"K11-K19","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":28,"title":["Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in-frame DICER1 deletion"],"prefix":"10.1093","volume":"178","author":[{"given":"Maria","family":"Apellaniz-Ruiz","sequence":"first","affiliation":[{"name":"1Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"2Department of Human Genetics, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"de Kock","sequence":"additional","affiliation":[{"name":"1Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"2Department of Human Genetics, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Sabbaghian","sequence":"additional","affiliation":[{"name":"1Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Guaraldi","sequence":"additional","affiliation":[{"name":"3Department of Biomedical and Neuromotor Sciences (DIBINEM), Pituitary Unit, IRCCS Institute of Neurological Sciences, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Ghizzoni","sequence":"additional","affiliation":[{"name":"4Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guglielmo","family":"Beccuti","sequence":"additional","affiliation":[{"name":"4Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D","family":"Foulkes","sequence":"additional","affiliation":[{"name":"1Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"2Department of Human Genetics, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"5Department of Oncology and Human Genetics, Program in Cancer Genetics, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"6Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"ref11","first-page":"1570","article-title":"Multinodular goiter","year":"2016","journal-title":"Endocrinology: Adult and Pediatric"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1002\/cam4.811","article-title":"Candidate microRNAs as biomarkers of thyroid carcinoma: a systematic review, meta-analysis, and experimental validation","volume":"5","year":"2016","journal-title":"Cancer Medicine"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1086\/301610","article-title":"Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer","volume":"61","year":"1997","journal-title":"American Journal of Human 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