A novel cause of type 1 von Willebrand disease: impaired exocytosis of Weibel-Palade bodies due to biallelic MADD variants.

ABSTRACT:

Abstract

The regulated secretion of von Willebrand factor (VWF) from Weibel-Palade bodies (WPBs) in endothelial cells is fundamental to hemostasis. This process relies on recruiting Rab GTPases and their effectors to the WPB membrane, with the guanine nucleotide exchange factor MAPK-activating death domain (MADD) playing a central role. Biallelic variants in MADD lead to a pleiotropic neurological and developmental disorder that can include bleeding abnormalities. This study investigates the impact of pathogenic MADD variants on VWF secretion using patient-derived endothelial cells. We isolated endothelial colony-forming cells (ECFCs) from 3 pediatric patients with biallelic MADD variants and unaffected heterozygous family members. All patients exhibited low VWF plasma levels (22-3

SUBMITTER: Hordijk S 

PROVIDER: S-EPMC12824698 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature