GNAQ pathways in port-wine stain

Port-wine stains are caused by somatic, mosaic mutations in the GNAQ gene. The pathogenic variant is usually a p.R183Q (c.G548A) mutation in guanine nucleotide binding protein alpha subunit q (GNAQ), primarily expressed in endothelial cells. This pathway shows predicted downstream targets of GNAQ that have been implicated in cell proliferation and survival, which leads to angiogenesis and capillary overgrowth. The resulting capillary malformation (CM) causes visibly pink, dark red, or purple discoloration of skin. Such "port wine stain" (PWS) of the skin is usually apparent at birth. It has a prevalence of 3-5 children per 1000 live births. PWS lesions, also known as nevus flammeus, are permanent but treatable by laser and topical therapies. In approximately 1 in 50,000 newborns, PWS is associated with Sturge-Weber syndrome (SWS), a more serious condition that has symptoms including glaucoma, seizures, and developmental delay. This diagram is based on figure 2 in Van Trigt et al. (2022).

脉络膜痣由GNAQ基因的体细胞镶嵌突变引起。致病的变异通常是GNAQ中鸟苷酸结合蛋白α亚基q（GNAQ）的p.R183Q（c.G548A）突变，主要在血管内皮细胞中表达。此通路展示了GNAQ的预测下游靶点，这些靶点与细胞增殖和存活相关，进而导致血管生成和毛细血管过度生长。由此产生的毛细血管畸形（CM）导致皮肤出现可见的粉红色、深红色或紫色斑点。这种皮肤上的“葡萄酒色斑”（PWS）通常在出生时即可明显。其发病率为每1000例活产婴儿中3-5例。PWS病灶，也称为火焰痣，是永久性的但可以通过激光和局部疗法进行治疗。在大约每50,000名新生儿中，PWS与Sturge-Weber综合征（SWS）相关联，这是一种更严重的疾病，其症状包括青光眼、癫痫发作和发育迟缓。本图基于Van Trigt等（2022）的图2。