EPAS1 gain-of-function syndrome and improper mesenchymal transition

Takeaway

  • This study further identified and characterized posterior fossa malformations and spinal dysraphism in patients with endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) gain-of-function syndrome. The pathogenesis of malformation and dysraphism in the mouse model also found evidence of persistent hypoxic signalling, persistent venous elements and failure of mesenchymal transition.

Why this matters

    This study further supports a common mechanism for posterior fossa and spinal malformations in EPAS1 gain-of-function syndrome and establishes the role of hypoxia-inducible factor-2α (HIF-2α) in their pathogenesis.