Disease for patient 1: Von Willebrand Disease Type1, transmitter VWD-type 3

Disease for patient 2: Von Willebrand Disease Type 3

Patient1: 90 YO female (Afro-Caribbean)

Patient2: 40 YO female (Afro-Caribbean)

Notes multiple variants in the VWF gene but have focused on variants in the D4 domain. However cannot discount the impact of some other variants.

Variant 1: VWF NM_000552.5: c.6647del p.(Cys2216Phefs*9), results in VWF protein missing D4 domain and C-terminal end of molecule

Phenotype patient 1: Reduced VWF levels in VWF:Ag, VWF:ristocetin cofactor, FVIII:C, FVIII(VWF:FVIIIB). Bleeding score 0, required Helixate treatment before and after receiving surgery.

Variant 2: VWF NM_000552.5: c.6432dup p.(Pro2145Thrfs*5)

Three sequence variations in family study showed other variants highlighted p.(Cys1149Arg) and p.(Pro2145Thrfs*5) are not on the same allele.

Does have other variants in VWF but they are stated by authors to not be detrimental. p.(Val510=) is noted to be potentially deleterious.

Phenotype patient 2: severely reduced VWF levels, absence of multimers, bleeding score 32, epistaxis, bruising, oral cavity bleeding, prolonged bleeding from minor wounds, menorrhagia, hemarthrosis, ankle arthropathy.

Suggests premature termination codons in these variants may lead to NMD but that this mechanism was found to be PTC position-dependent. Degradation was not 100% and need to perform cellular experiments.

GeneName: DICER1 PMCID: PMC7859642 HGNCID: Unavailable Inheritance Pattern: Autosomal dominant. Disease Entity: Familial pleuropulmonary blastoma (PPB), cervix embryonal rhabdomyosarcoma, multinodular goiter, nasal chondromesenchymal hemartoma, Ciliary body medulloepithelioma, Sertoli-Leydig Cell Tumor (SLCT), differentiated thyroid carcinoma, pituitary blastoma, pineoblastoma, cystic nephroma, Wilm's tumor and sarcomas of different sites including, amongst others, the uterine cervix, kidney and brain. Mutation: Germline Zygosity: Heterozygose Variant: No ClinVarID present. Family Information: No family outline Case: No specified information of patients included. CasePresentingHPO's: n/a CasePrevious Testing: n/a gnomAD: n/a Mutation Type: nonsense, frameshift, or splice affected.