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

Area of Science:

• Vascular biology
• Developmental biology
• Genetics

Background:

• Capillary malformations (CM) are congenital vascular anomalies affecting skin, brain, and eyes.
• Sturge-Weber Syndrome (SWS) involves CM in multiple tissues.
• A common somatic mutation, GNAQ (p.R183Q), drives CM pathogenesis.

Purpose of the Study:

• To investigate the distinct morphological characteristics of CM in brain and skin.
• To understand the role of the GNAQ p.R183Q variant in CM development.
• To identify potential tissue-specific therapeutic targets for CM.

Main Methods:

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

Main Results:

• CM vessels in both tissues were enlarged with fibrin leakage and reduced zona occludin-1.
• Macrophage infiltration (MRC1+/LYVE1+) was observed around CM vessels.
• Differences in endothelial sprouting and mural cell localization were noted between brain and skin CMs.

Conclusions:

• CMs exhibit shared and distinct features in the brain and skin.
• Understanding these differences is crucial for developing targeted therapies.
• The GNAQ p.R183Q variant is a key driver of CM formation.