FOXM1 c.1205 C > A mutation is associated with unilateral Moyamoya disease and inhibits angiogenesis in human brain endothelial cells.

Unilateral moyamoya disease (MMD) represents a distinct subtype characterised by occlusive changes in the circle of Willis and abnormal vascular network formation. However, the aetiology and pathogenesis of unilateral MMD remain unclear. In this study, genetic screening of a family with unilateral MMD using whole-genome sequencing helped identify the c.1205 C > A variant of FOXM1, which encodes the transcription factor FOXM1 and plays a crucial role in angiogenesis and cell proliferation, as a susceptibility gene mutation. We demonstrated that this mutation significantly attenuated the proangiogenic effects of FOXM1 in human brain endothelial cells, leading to reduced proliferation, migration, and tube formation. Furthermore, FOXM1 c.1205 C > A results in increased apoptosis of human brain endothelial cells, mediated by the downregulation of the transcription of the apoptosis-inhibiting protein BCL2. These results suggest a potential role for the FOXM1 c.1205 C > A mutation in the pathogenesis of unilateral MMD and may contribute to the understanding and treatment of this condition.