3 Matching Annotations
  1. May 2022
    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
  2. Apr 2022
    1. DICER1 syndrome is an autosomal-dominant, pleiotropic tumor-predisposition disorder

      Gene Name:DICER1 PMID: 30715996 HGNCID: Not on document Inheritance Pattern: Autosomal Dominant Disease Entity: Pleiotropic Tumor-Predisposition Disorder Mutation: Pathogenic Germline Variants Zygosity: Not in document Variant: Not in document Family Information: An individual was found who had family members who were also affected by this mutation. Because of this, those family members were also chosen to participate in this study. Mutation Type: Missense Case: The study was done on more than one individual. Roughly more than half of the individuals were female

    1. The DICER1 syndrome is an autosomal dominant tumor‐predisposi-tion disorder associated with pleuropulmonary blastoma, a rare pediatric lung cancer

      GeneName:DICER1 PMID (PubMed ID): PMCID: PMC6418698 PMID: 30672147 HGNCID: NOT LISTED<br /> Inheritance Pattern: Autosomal Dominant Disease Entity: Cancer; benign and malignant tumors including pleuropulmonary blastoma, cystic nephroma, Sertoli-Leydig cell tumors, multinodular goiter, Thryoid cancer, rhabdomyosarcoma, and pineoblastoma. Mutation: Somatic missense variation Mutation type: missense Zygosity: None stated Variant: unregistered…. Family Information: Characterize germline variants in familial early-onset clorectal cancer patients; The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation. CasePresentingHPOs: uterine and rectal cancers in germline mutation