Silent disruption: Aberrant splicing in VWD

Abstract

In this issue of Blood, Yadegari et al1 report in a patient with type 1 von Willebrand disease (VWD) a novel synonymous von Willebrand factor (VWF) genetic variant and aberrant VWF splicing mechanism leading to VWF mRNA intron retention. The index patient presented with mucosal and provoked bleeding and low VWF level (VWF:Ag) and activity (VWF:GPIb) of 9 and 6 IU/dL, respectively. She also had a normal VWF multimer pattern and had a poor response to desmopressin. This is consistent with qualitatively normal VWF but low VWF due to defective VWF production and/or storage. Neither parent had a history of significant bleeding, but each had borderline-to-low VWF:Ag levels (49 and 44 IU/dL) and similarly low VWF:GPIb levels.