9 Matching Annotations
  1. Oct 2024
    1. Disease: Von Willebrand Disease (VWD) type 1

      Patient(s): 13 yo, female and 14 yo, female, both Italian

      Variant: VWF NM_000552.5: c.820A>C p. (Thr274Pro)

      Dominant negative effect

      Heterozygous carrier

      Variant located in the D1 domain on VWF

      Phenotypes:

      heterozygous carriers have no bleeding history

      reduced VWF levels compatible with diagnosis of VWD type 1

      increased FVIII:C/VWF:Ag ratio, suggests reduced VWF synthesis/secretion as possible phathophysiological mechanism

      Normal VWFpp/VWF:Ag ratio

      Modest alteration of multimeric pattern in plasma and platelet multimers

      plasma VWF showed slight increase of LMWM and decrease of IMWM and HMWM

      Platelet VWF showed quantitative decrease of IMWM, HMWM, and UL multimers

      In silico analysis:

      SIFT, ALIGN, GVD Polyphen 2.0, SNP&GO, Mutation Taster, Pmut all suggest damaging consequences.

      PROVEAN and Effect suggest neutral effect

      according to ACMG guidelines this variant was classified as pathogenic

  2. Sep 2024
    1. In silico analysis of pathogenicity

      4 in silico prediction softwares classify as benign

      Mentions according to ACMG guidelines classify variant as VUS initially

      later reclassified as pathogenic

  3. Aug 2022
  4. 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 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

  5. Apr 2022
    1. Health care providers may consider the presence of DICER1 pathogenic variants when a female presents with a personal or family history of ovarian sex cord-stromal tumor

      FAMILY INFORMATION: FEMALE PATIENTS WITH A PERSONAL OR FAMILY HISTORY OF OVARIAN TUMORS

  6. Mar 2022
  7. Jan 2022
    1. I went to Portland, Oregon, to interview Prof Joel Nigg, who is one of the leading experts in the world on children’s attention problems, and he told me we need to ask if we are now developing “an attentional pathogenic culture” – an environment in which sustained and deep focus is harder for all of us.

      : attentional pathogenic culture ; an environment in which sustained and deep focus is harder for all of us

  8. Feb 2021