Similarities and differences between brain and skin GNAQ p.R183Q driven capillary malformations

Area of Science:

• Vascular Biology
• Genetics
• Dermatology

Background:

• Capillary malformations (CM) are congenital vascular anomalies affecting skin, brain, and eyes, particularly in Sturge Weber Syndrome (SWS).
• A recurrent somatic mutation (GNAQ p.R183Q) is identified in approximately 90% of CM specimens, driving disease pathogenesis.
• Endothelial GNAQ p.R183Q expression in mice is sufficient to induce CM-like vascular changes.

Purpose of the Study:

• To investigate and compare the morphological characteristics of capillary malformations in brain and skin tissues.
• To understand the distinct pathogenic mechanisms underlying CM in different anatomical locations.
• To identify potential therapeutic targets for both syndromic and non-syndromic CM.

Main Methods:

• Morphological analysis of CM specimens from brain and skin.
• Droplet digital PCR to quantify GNAQ p.R183Q allelic frequency.
• Immunohistochemical staining for endothelial cells, tight junctions, mural cells, and macrophages.

Main Results:

• CM vessels in both brain and skin showed enlargement, fibrin leakage, and reduced tight junction proteins (zona occludin-1, claudin-5).
• Macrophage infiltration (MRC1+/LYVE1+) was observed around CM vessels in both tissues.
• Significant differences were noted in endothelial sprouting activity and mural cell localization between brain and skin CMs.

Conclusions:

• CMs share common vascular features but exhibit tissue-specific differences in pathogenesis.
• Understanding these distinct characteristics is crucial for developing targeted, tissue-specific therapies for CM.
• Further research into these differences may lead to novel treatment strategies for SWS and non-syndromic CM.