Novel Genetic Mutations in a Sporadic Port-Wine Stain

Abstract

IMPORTANCE Port-wine stains (PWSs) are common congenital cutaneous capillary malformations. A somatic GNAQ mutation was recently identified in patients with sporadic PWSs and Sturge-Weber syndrome. However, subsequent studies to confirm or extend this observation are lacking.OBSERVATIONS We report a long-standing, unilateral facial PWS of a man in his early 70s confirmed by histopathological analysis. Staged surgical excision of the vascular malformation was performed, and genomic DNA was extracted from the vascular malformation specimen and normal skin. Targeted next-generation sequencing of the coding sequence of 275 known cancer genes including GNAQ was performed in both specimens. A single-nucleotide variant(c.548G>A, p.Arg183Gln) in GNAQ was identified in the PWS-affected tissue but not in the normal skin sample. In addition, this sequencing approach uncovered several additional novel somatic mutations in the genes SMARCA4, EPHA3, MYB, PDGFR-β, and PIK3CA.CONCLUSIONS AND RELEVANCE Our findings confirm the presence of somatic mutations inGNAQ in the affected skin of a patient with congenital PWS, as well as alterations in several other novel genes of possible importance in the pathogenesis of PWS that may also offer substantial therapeutic targets.

The somatic GNAQ mutation (R183Q) is primarily located within the blood vessels of port wine stains

“…1 A sporadic somatic guanine nucleotide-binding protein, G alpha subunit q (GNAQ) mutation (R183Q) has been identified in PWS lesions. 2, 3 However, the cell-type specific distributions of the GNAQ mutation (R183Q) in PWS lesions have yet to be determined.…”

Somatic GNAQ Mutation is Enriched in Brain Endothelial Cells in Sturge–Weber Syndrome

“…Recent genetic studies discovered a somatic mosaic mutation in GNAQ (c.548G>A; p.R183Q) in SWS brain and skin lesions and non-syndromic capillary malformation lesions 6–8 . GNAQ encodes Gαq, an alpha subunit of heterotrimeric G proteins.…”

Activation of PKCα and PI3K Kinases in Hypertrophic and Nodular Port Wine Stain Lesions

“…Recent studies have suggested that sporadic somatic mutations of guanine nucleotide-binding protein, G alpha subunit q ( Gnaq ) (R183Q) and phosphatidylinositol 3-kinase catalytic, alpha polypeptide ( Pi3kca ) are linked to the vascular phenotypes of PWS. 12–14 Shirley et al 13 first discovered a low-frequency somatic mutation in the Gnaq gene (c.548 G→A, p.R183Q) present in PWS lesions. We and Cuoto et al further identified that Gnaq (R183Q) is primarily present in blood vessels (60%) 15,16 and/or in connective tissue (30%) 16 and hair follicle/glands (20%) 16 in PWS lesions.…”