# Somatic TEK Mutation Identified in a Patient with Calvarial Venous Malformations

## TL;DR

A new somatic TEK mutation was found in a teenager with a rare scalp and skull venous malformation, suggesting genetic testing could help diagnose similar cases.

## Contribution

The first reported case of a pediatric calvarial venous malformation linked to a novel somatic TEK L914F mutation.

## Key findings

- A novel somatic TEK L914F mutation was identified in lesional DNA but absent in germline DNA.
- Single-cell RNA sequencing showed TEK enrichment in endothelial cells and implicated angiogenesis and PI3K/Rho signaling pathways.
- The findings suggest TEK mutations contribute to diverse venous malformations and highlight the need for genetic testing in sporadic cases.

## Abstract

Background: Calvarial venous malformations (VMs) are rare and genetically understudied. While somatic TEK receptor tyrosine kinase (TEK) mutations drive sporadic VMs, their role in scalp–calvarial VMs is unknown. We report the first pediatric case of a calvarial VM with a pathogenic somatic TEK mutation and its molecular implications. Methods: A 16-year-old female with a symptomatic parietal scalp VM underwent neurosurgical resection. Exome sequencing was performed on both lesional and blood DNA. Single-cell RNA sequencing (scRNA-seq) data from normal brain vasculature were analyzed for TEK expression and pathway enrichment. Results: A novel somatic TEK L914F mutation (chr9:27212760-C-T [GRCh38]), absent in germline DNA and population databases, was identified and predicted to be deleterious (CADD: 24). scRNA-seq data analysis revealed TEK enrichment in endothelial cells, particularly in fetal and arterial subtypes, and implicated angiogenesis and PI3K/Rho signaling as potential downstream phenotypic and molecular consequences. Conclusions: This first pediatric scalp VM with a somatic TEK L914F mutation expands the phenotypes associated with TEK-related vascular anomalies. These findings emphasize the role of somatic TEK mutation in diverse VMs and support genetic testing in sporadic cases. Further studies are needed to define therapeutic targets.