In a collaborative basic research, we identified a novel mutation V1499E with a high penetrance in a large Dutch family with autosomal dominant type 2A vWD, which was detected independently in 3 hospitals and academic coagulation laboratories (Table 4).24
Case: Dutch Family Proband (II-1), male
DiseaseAssertion: VWD2A
FamilyInfo: 10 additional affected family members (phenotypic details in Table 4)
ParentalGenotype(s): NA
CasePresentingHPOs: HP:0030132, HP:0011871, HP:0012147, HP:0030129
(Absence of large von Willebrand factor multimers, Impaired RIPA, Reduced quantity of VWF, Impaired ristocetin cofactor assay activity)
CaseHPOFreeText: FVIII:C = 63, vWF:Ag = 59, vWF:pp = 76, pp/Ag = 1.3, vWF:RCo = <15, Rco/Ag = 0.30, RIPA = N; minor or poor response to DDAVP of functional vWF:RCo and vWF:CB with no correction of vWF multimers and BT directly after DDAVP
CaseNOTHPOs:
CaseNOTHPOFreeText:
CasePreviousTesting: NA
GenotypingMethod: NA
PreviouslyPublished: PMID: 19346881
Gene: VWF
Variant: c.4496T>A (p.Val1499Glu)
HGVS: NM_000552.4(VWF):c.4496T>A (p.Val1499Glu)
ClinVarID: 440408; https://www.ncbi.nlm.nih.gov/clinvar/variation/440408/
CAID:
gnomAD: absent