Premature termination codon mutations in the von Willebrand factor gene are associated with allele-specific and position-dependent mRNA decay
PMID: 19773258
Notes: c.2546+3G>C variant with confirmed splicing impact, exon 19 skipping and premature stop codon in exon 20 leading to NMD. Lab values are borderline normal and not inclusive of values needed for type 2N
CAID: CA2013880906
PatientDetails: more detailed proband and proband father lab values are in the supplementary data
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).