5 Matching Annotations
  1. May 2022
    1. DICER1 syndrome encompasses a variety of benign and malignant manifestations including multinodular goitre

      Gene: DICER1 PMCID: PMC8451242 PMID: 34552563 Pathogenic Inheritance Pattern: Autosomal Dominant MultipleDiseaseEntities Disease Entity: DICER1 syndrome, multinodular goitre, cystic nephroma, anaplastic renal sarcoma, Wilms tumour, differentiated thyroid carcinoma, gynandroblastoma, ciliary body medulloepithelioma, embryonal rhabdomyosarcoma, pineoblastoma, pituitary blastoma, kidney cyst, pulmonary cyst, Sertoli-Leydig Cell Tumor. Mutation: Germline MultipleGeneVariants Variant & Clinvar IDs: c.3452_3453del (485534), c.316del (no ClinVar ID), c.171_172insAC (no ClinVar ID), c.3434del (no ClinVar ID), c.988C>T (933007), c.5388dup (no ClinVar ID) Zygosity: None provided. Case: At time of operation, the goitre patients living in Denmark were ages 21, 12, 21, 8, 14, and 16. Four underwent total thyroidectomies, and two underwent partial thyroidectomies. The patient originally aged 21 previously had a kidney cyst at age 14 and a pulmonary cyst at an unknown age. The patient aged 14 at time of partial thyroidectomy later manifested a Sertoli-Leydig Cell Tumor at age 15. All six patients were female. CasePresentingHPO: None provided. CasePreviousTesting: thyroidectomy gnomAD: ENSG00000100697.10, https://gnomad.broadinstitute.org/gene/ENSG00000100697 Mutation Type: Frameshift, Nonsense

    1. DICER1 gene is located on chromosome 14q32.13 and plays a crucial role in the control of protein translation; its product, dicer protein, is a ribonuclease (RNase) III endoribonuclease which is essential for the production of microRNAs (miRNA) which are formed by the cleavage of pre-miRNA or double-stranded RNA1–4. RNase III contains two domains, IIIa and IIIb which cleave 3p miRNA and 5p miRNA from the 3′ and 5′ pre-miRNA, respectively. These cleavages require magnesium ions at the interface between the IIIa and IIIb domains and the miRNA; this magnesium dependent catalytic processing occurs at specific residues, E1320, E1564, E1813 and D17092–4. miRNA has a pivotal role in regulating the expression of over 30% of protein-coding genes by its interaction with mRNA5. Given the impact of DICER1 in post-translational events, it is not entirely surprising that functional DICER1 is essential for vertebrate development as evidenced by developmental arrest and death of the embryo when both alleles are lost6,7. Conceptually, DICER1 can be regarded as either a tumor suppressor gene due to loss-of-function mutations or an oncogene due to gain-of-function mutations; it is thought to function as a haploinsufficient tumor suppressor gene with the loss of one allele leading to tumor progression but loss of both alleles having an inhibitory effect for tumor development implying that one intact allele is needed for cell survival8.A study led by one of the authors (DAH) identified germline loss-of-function DICER1 mutations affecting the RNase IIIb domain in affected families with pleuropulmonary blastoma (PPB)9, a rare dysembryonic lung malignancy of childhood which was not the only manifestation of this familial tumor predisposition syndrome; germline and somatic DICER1 mutations were subsequently identified in several other familial associated tumors in several extrapulmonary sites (Table 1). Individuals with germline DICER1 mutations also had non-neoplastic conditions including macrocephaly, renal structural anomalies, retinal abnormalities, dental perturbations, and the GLOW syndrome (global developmental delay, lung cysts, overgrowth and Wilms tumor). These associations encircle the DICER1 tumor predisposition syndrome (Online Mendelian Inheritance in Man numbers 606241, 601200 and 138800), with the estimation that 90% of those affected by this syndrome inherited a germline mutation from one of their parents, with a pattern of autosomal dominant inheritance10.
      • Gene Name: DICER1 Syndrome (OMIM 606241, 601200)
      • PMID: 34599283
      • Hugo Gene Nomenclature Committee (HGNCID): N/A
      • Inheritance Pattern: Autosomal Dominant
      • Disease Entity: pleuropulmonary blastoma (PPB), Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations.
      • Mutation: Germline
      • Zygosity: Heterozygous
      • Variant: has multiple variants associated with it
      • Family Information: Germ cell tumors have been reported in family members
      • Case: identified affected families w/ pleuropulmonary blastoma (PPB): germline and somatic DICER1 mutations also identified in other familial associated tumors
      • CasePreviousTesting: numerous studies confirmed relationship b/t DICER1 variants in carriers and development of range neoplasms and non-neoplastic conditions
    1. DICER1 syndrome is an autosomal-dominant, familial pleiotropic tumor-predisposition disorder1 caused by pathogenic germline variants in DICER1, an essential component of the microRNA processing pathway.

      GeneName: DICER1 PMID: 30715996 HGNCID: N/A Inherritence pattern: autosomal dominant Disease Entity: multiple gene variants mutation: germline Zygosity: N/A Variant: Not found Family Info: N/A

  2. Apr 2022
    1. The DICER1 syndrome

      Gene: DICER1 PMID: 30672147 HGNCID: n/a Inheritance Pattern: autosomal dominant Disease Entity: Pleuropulmonary Blastoma, Cystic Nephroma, Sertoli-Leydig tumors, Multinodular goiter, thyroid cancer, rhabdomysarcoma, pineoblastoma Mutation: Germline Zygosity: n/a MultipleGeneVariants Variant: p.Gly1824Val, p.Ser1160Tyr, p.Ala1578Thr, p.Leu1469Pro, p.Ser1160Tyr, p.Ile528Thr, p.Pro1836Leu, p.Glu904*, p.Tyr1835Ser, p.Ile528Thr, p.Arg1342His, p.Phe1650Cys, p.Trp1481Arg, p.Arg201His, p.Asp1390His, p.Trp1397Arg, p.Ala1578Thr <br /> Family Info: n/a gnomAD: n/a

    1. DICER1 syndrome (OMIM 606241, 601200)

      Gene Name: OMIN PMID: 34599283 Autosomal Dominant Gynandroblastoma cERMS Pediatric Paratesticular Sarcomas nephrolithiasis or nephrocalcinonsis Cystic Nephroma Anaplastic Sarcoma of Kidney Wilms tumor Cystic Hepatic Neoplasm Hamartomatous polyps

      Germline mutation heterozygosity Multiple Gene Variants There is usually a family history or a carrier for the mutation it rarely occurs out of nowhere.