Disease: Von-willebrand Disorder (2N)

Patient: 32 yo, male

Variant: VWF NM_000552.5 c:2527C>T, p.(Arg760Cys), exon 17, noted to be dominant effect

Note: Proband also has an Arg91Gln mutation in exon 20 of VWF too.

Phenotypes: Mild bleeding history, epistaxis, bleeding gums, bleeding after tooth extraction. 11 years old had severe hemorrhage following tonsillectomy. Previous diagnosis of hemophilia A.

Family: father has history of epistaxis but never eamined prior to study. Father has the Arg760Cys mutation at heterozygous level. Mother is asymptomatic and classified as hemophilia A carrier following hemophilia A diagnosis in son. Mother also has the Arg91Gln mutation in exon 20 at heterozygous level.

Molecular Phenotypes: mild decrease in plasma FVIII and VWF levels, normal platelet VWF content, decreased FVIII binding capacity of VWF. Causes retention of pro-VWF(suggest defects in the maturation process of VWF). Abnormal VWF and platelet GPIb interaction(documented by impaired or absent RIPA and decreased VWF:RCo).