Case#: 2D

DiseaseAssertion:

FamilyInfo: Her son 2E had mild bruising and epistaxis.

CaseHPOFreeText: The proposita (2D) in family 2 was investigated after a postpartum hemorrhage requiring blood transfusion. She gave a longstanding history of menorrhagia, and her calculated bleeding score was 10, the highest of all the persons in this study. VWF:Ag, VWF:RCo, and multimer analysis were all normal. VWF:CB was significantly reduced with both types I and III collagen, resulting in CB:Ag ratios of 0.2 to 0.4. Closure times in the PFA-100 were normal in 2D with both cassettes (Coll/Epi, 111 seconds; Coll/ADP, 98 seconds). The discrepant reduction in VWF:CB persisted after DDAVP administration to 2D despite normalization of both VWF:Ag and VWF:CB (samples taken 90 minutes after DDAVP administration showed VWF:Ag 191 IU/dL, VWF:CB 67 IU/dL, CB:Ag ratio = 0.35).

CasePreviousTesting: Fifty-one primer sets were used to amplify the essential regions of VWF (52 exons, flanking intronic regions, 5′ promoter region, and the 3′ untranslated region).

Gene: VWF

Variant: Her and son were shown to be heterozygous for a novel mutation in exon 31:c.5347 T → G resulting in Ser1783Ala

HGVS: NM_000552.5(VWF):c.5347T>G (p.Ser1783Ala)

ClinVar: 31012

CAID: CA228715

gnomAD: 0.0006918 in south asian pop

Case#: 32 year old female

DiseaseAssertion: VWD Type 2M

CaseHPOFreeText4: Testing was repeated multiple times, with initial results being untrustworthy. Follow up testing is as follows: VWF:RCo/VWF:Ag ratio = 0.61, VWF:CB = 10. Normal multimers

CasePreviousTesting: Molecular analysis by next generation gene sequencing analysis of VWF, F8, GPIBA and GPIBB.

Gene: VWF

Variant: variant in VWF at exon 31 (c.5347 T > G) that leads to a VWF protein change of p.Ser1783Ala

HGVS: NM_000552.5(VWF):c.5347T>G (p.Ser1783Ala)

ClinVar: 31012

CAID: CA228715

gnomAD: 0.0006918 in South Asian pop