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

4 in silico prediction softwares classify as benign

Mentions according to ACMG guidelines classify variant as VUS initially

later reclassified as pathogenic

Yates, C., & Feil, E. (2021, February 1). Will coronavirus really evolve to become less deadly? The Conversation. http://theconversation.com/will-coronavirus-really-evolve-to-become-less-deadly-153817

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

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

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

CBC Podcasts. (2022, February 3). Today on #TheDoseCBC: a frank discussion about the new #Omicron sub-variant with virologist @angie_rasmussen, who says BA.2 isn’t necessarily more pathogenic—But we need to proceed with caution. Learn more: Http://bit.ly/3gnlPak https://t.co/NOp7MMwkwk [Tweet]. @cbcpodcasts. https://twitter.com/cbcpodcasts/status/1489315238822490118

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

Gordon, D. E., Hiatt, J., Bouhaddou, M., Rezelj, V. V., Ulferts, S., Braberg, H., Jureka, A. S., Obernier, K., Guo, J. Z., Batra, J., Kaake, R. M., Weckstein, A. R., Owens, T. W., Gupta, M., Pourmal, S., Titus, E. W., Cakir, M., Soucheray, M., McGregor, M., … Krogan, N. J. (2020). Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science, 370(6521). https://doi.org/10.1126/science.abe9403