Novel <i>DICER1</i> mutation as cause of multinodular goiter in children

Darrat, Ilaaf; Bedoyan, Jirair K.; Chen, Ming; Schuette, Jane L.; Lesperance, Marci M.

doi:10.1002/hed.23250

Cited by 28 publications

(17 citation statements)

References 23 publications

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“…In case 2, germline testing of the patient's blood‐derived DNA revealed a premature truncating mutation (c.1525C > T p.R509Ter) in DICER1 (Table 1). 19 We identified two distinct DICER1 hotspot mutations, c.5438A> C, p.E1813A and c.5113G> A, p.E1705K, in the left and right ovarian tumours, respectively (Table 1). 14 …”

Section: Resultsmentioning

confidence: 91%

“…Patients with germline mutations have DICER1 syndrome. As well as SLCT, these patients are also predisposed to develop a wide range of other ‘hyperplastic’ disorders and uncommon neoplasms; these include lung cysts, thyroid multinodular goitre, various benign and malignant thyroid neoplasms, pleuropulmonary blastoma, cystic nephroma, anaplastic sarcoma of the kidney, ciliary body medulloepithelioma, nasal chondromesenchymal hamartoma, pituitary blastoma, pineoblastoma, and embryonal rhabdomyosarcoma of the cervix, ovary, fallopian tube, and genitourinary tract 9,12–20 …”

Section: Introductionmentioning

confidence: 99%

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Somatic tumour testing establishes that bilateral DICER1‐associated ovarian Sertoli–Leydig cell tumours represent independent primary neoplasms

et al. 2020

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Aims Sertoli–Leydig cell tumours (SLCTs) are rare ovarian neoplasms that are commonly associated with somatic or germline DICER1 mutations, especially when of the moderately or poorly differentiated type. A large majority are unilateral, but bilateral neoplasms have been reported, sometimes in the context of germline DICER1 mutations (DICER1 syndrome). It is currently unknown whether these represent independent neoplasms or metastasis from one ovary to the other and we aimed to elucidate this. Methods and results We report three cases of bilateral ovarian SLCT (all in patients with DICER1 syndrome) and review all reported cases of bilateral neoplasms. In the three cases (all moderately or poorly differentiated neoplasms), the time interval between the discovery of the tumours in each ovary ranged from 2.7 years to 6 years. In all cases, different DICER1 somatic hotspot mutations within the two tumours provided definitive proof that they represent independent neoplasms; this may be important clinically. Our literature review revealed that, when this information was available, all patients with bilateral SLCT had a germline DICER1 mutation. Conclusions Bilateral ovarian SLCTs represent independent rather than metastatic neoplasms, and essentially always occur in the context of DICER1 syndrome.

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Section: Resultsmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Somatic tumour testing establishes that bilateral DICER1‐associated ovarian Sertoli–Leydig cell tumours represent independent primary neoplasms

et al. 2020

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“…In 2011, Rio Frio and coworkers (6) identified germline mutations in DICER1 (on chromosome 14q32) as the cause of familial MNG with or without ovarian Sertoli-Leydig cell tumor (SLCT) (7), adding a new phenotype to the DICER1 syndrome (OMIM #601200). Since then, several articles have reported patients with germline DICER1 mutations who have MNG alone or in combination with other known DICER1-related diseases (8,9,10).…”

Section: Introductionmentioning

confidence: 99%

Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in-frame DICER1 deletion

Apellaniz-Ruiz

Kock

Sabbaghian

et al. 2018

European Journal of Endocrinology

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“…In support of previous studies exploring rare exclusive MNG families, 11,20 we confirmed that MNG/TD occurring in children and young adults should be used to identify DICER1-syndrome families and to perform cascade testing, genetic counselling and implement preventive strategies. This requires a close collaboration between oncologists and endocrinologists, from paediatrics to adulthood, to determine the true prevalence of thyroid disease in this syndrome.…”

Section: Discussionmentioning

confidence: 99%

Multinodular goitre is a gateway for molecular testing of DICER1 syndrome

Oliver‐Petit¹,

Bertozzi

Grunenwald

et al. 2019

Clinical Endocrinology

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Background DICER1 syndrome is an autosomal dominant disorder that predisposes individuals to develop benign or malignant tumours from infancy to adulthood. There is low‐to‐moderate penetrance of tumour development, which is sex‐ and age‐dependent. Multinodular goitre (MNG) is among the most highly penetrant phenotype of the disorder, especially in females. Patients and Methods We report a series of eight families referred for childhood‐onset of MNG or DICER1‐related 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 DICER1 variants using Next Generation Sequencing tools. Results Germline pathogenic DICER1 gene variants were identified in all probands and several of their relatives: 64% presented with MNG/thyroidectomy as the phenotypic expression of the syndrome. DICER1 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 DICER1 variant carriers has permitted diagnosis and therapeutic scheme correction for two patients and cascade testing in relatives. Conclusions Multinodular goitre is uncommon in children. Childhood‐onset 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 DICER1 gene, as proposed by recent international recommendations. Early detection of DICER1 pathogenic variants has important consequences in terms of therapeutic strategy, early tumour screening, and genetic counselling.

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Novel DICER1 mutation as cause of multinodular goiter in children

Cited by 28 publications

References 23 publications

Somatic tumour testing establishes that bilateral DICER1‐associated ovarian Sertoli–Leydig cell tumours represent independent primary neoplasms

Somatic tumour testing establishes that bilateral DICER1‐associated ovarian Sertoli–Leydig cell tumours represent independent primary neoplasms

Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in-frame DICER1 deletion

Multinodular goitre is a gateway for molecular testing of DICER1 syndrome

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