Preprint: de novo GABPA variant identified as candidate cause of novel congenital vascular anomaly

A bioRxiv preprint reports the genomic characterisation of a previously unclassified congenital vascular anomaly in a single patient presenting with multifocal cutaneous vascular tumours. Through comprehensive genomic analysis, the authors identified a novel heterozygous de novo germline variant in GABPA, which encodes GA-binding protein-alpha, a member of the ETS family of transcription factors.

Histopathological assessment revealed capillary-venous lesions that lacked expression of glucose transporter 1 (GLUT1), a feature that distinguishes this entity from infantile haemangioma. The tumour vasculature showed a prominent layer of alpha-smooth muscle actin (alpha-SMA)-positive perivascular cells, and nuclear localisation of GABPA was noted in the affected tissue.

The findings propose GABPA as a candidate disease gene for this unclassified vascular anomaly and contribute to the expanding literature on transcription factor variants underlying congenital vascular malformations. Because this is a single-patient report and a preprint not yet subject to peer review, replication in additional affected individuals will be needed to establish causality.

The study is primarily of interest to researchers in vascular biology and developmental genetics, and to genetic counsellors with an interest in rare congenital anomalies and de novo variant interpretation.