DICER1 is the only miRNA biogenesis component associated with an inherited tumor syndrome, featuring multinodular goiter (MNG) and rare pediatric-onset lesions.
In this report, we describe DICER1 gene analysis in an adolescent diagnosed with multinodular goiter, ovarian Sertoli-Leydig cell tumor, and lung cyst.
A nonsense germ-line mutation in DICER1 causing a truncated protein at the IIIb domain level was identified segregating within a family including two affected relatives who developed in one case cystic nephroma and pleuropulmonary blastoma, and rhabdomyosarcoma and multinodular goiter in the other.
DICER1 germline mutation carriers have an increased predisposition to cancer, such as pleuropulmonary blastoma (PPB) and Sertoli-Leydig cell tumor (SLCT), and a high prevalence of multinodular goiter (MNG).
Here, we present a 16-year-old Chinese adolescent suffering from an ovarian Sertoli-Leydig cell tumor,well-differentiated fetal adenocarcinoma of the lung, and familial multinodular goiter with a nonsense mutation (c.3540C > A; p.Tyr1180*) in exon 21 of DICER1.
In a child with a SLCT and MNG, and in her mother and brother (both diagnosed with MNG), we identified a heterozygous germ-line deletion of approximately 3 kilobases that eliminates exon 21 of DICER1 and two-thirds of intron 21, accompanied by an insertion of a G nucleotide at the 3' end of the deletion (c.3270-6_4051-1280delinsG).
Thyroid abnormalities are a common finding in DICER1 syndrome with multinodular goiter frequently present in many families in which a germline DICER1 mutation is segregating.
Forty different heterozygous germline DICER1 mutations have been reported worldwide in 42 probands that developed as children or young adults, pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian sex cord-stromal tumors (especially Sertoli-Leydig cell tumor [SLCT]), and/or multinodular goiter (MNG).
Linkage analysis of candidate genes in autoimmune thyroid disease. III. Detailed analysis of chromosome 14 localizes Graves' disease-1 (GD-1) close to multinodular goiter-1 (MNG-1). International Consortium for the Genetics of Autoimmune Thyroid Disease.
A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at the same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary).
Thyroid stimulating hormone receptor (TSHR) is thought to play a critical role in the pathogenesis of certain thyroid diseases, including Graves' disease (GD), multinodular thyroid goiter (MTG), and Hashimoto's thyroiditis (HT).
The aim of the study was to investigate whether the mutations of the GNAS gene and thyroid-stimulating hormone receptor (TSHR) gene were a potential molecular biological mechanism for subclinical toxic multinodular goiter (sTMG) and to evaluate the association of these mutations with the clinicopathological features of these disorders.Forty-four patients with sTMG and 20 controls(multinodular goiter) from Heilongjiang province of China who underwent subtotal thyroidectomy were recruited.