A somatic missense mutation in GNAQ causes capillary malformation.
A somatic missense mutation in GNAQ causes capillary malformation.
复制标题
DOI：
10.1097/moh.0000000000000500
复制
发表时间：
2019-05
影响因子：
3.2
通讯作者：
Bischoff J
中科院分区：
文献类型：
--
作者：
Bichsel C;Bischoff J
毛细血管畸形（CM）是最常见的血管畸形类型，是由GNAQ的体细胞镶嵌突变引起的，该突变编码异三聚体g蛋白的Gαq亚基。预测激活g - α - q的单一氨基酸变化是如何引起CM的尚不清楚，但最近的进展有助于揭示其机制。GNAQ R183Q突变存在于从皮肤和脑CMs分离的内皮细胞中，但也存在于CM底层的脑组织中，这引发了关于CM引起细胞起源的问题。计算分析揭示了本构激活的机制，新的基础科学表明Gαq在感知剪切应力和调节脑血流中发挥作用。一些研究证实，GNAQ R183Q突变存在于90%的非综合征和SWS综合征CMs中。这种突变在从皮肤、大脑和脉络膜CMs中分离出来的内皮细胞和血管中富集，但这种突变是否存在于其他类型的细胞中必须确定。此外，必须揭示R183Q突变改变微血管结构和血流的机制，以开发新的治疗策略，特别是SWS，这是一种无法治愈的毁灭性疾病。
Capillary malformations (CM), the most common type of vascular malformation, are caused by a somatic mosaic mutation in GNAQ, which encodes the Gαq subunit of heterotrimeric G-proteins. How the single amino acid change – predicted to activate Gαq - causes CM is not known but recent advances are helping to unravel the mechanisms. The GNAQ R183Q mutation is present in endothelial cells isolated from skin and brain CMs, but also in brain tissue underlying the CM, raising questions about the origin of CM-causing cells. Insights from computational analyses shed light on the mechanisms of constitutive activation and new basic science shows Gαq plays roles in sensing shear stress and in regulating cerebral blood flow. Several studies confirm the GNAQ R183Q mutation in 90% of non-syndromic and Sturge-Weber syndrome (SWS) CMs. The mutation is enriched in endothelial cells and blood vessels isolated from skin, brain and choroidal CMs but whether the mutation resides in other cell types must be determined. Further, the mechanisms by which the R183Q mutation alters microvascular architecture and blood flow must be uncovered to develop new treatment strategies for SWS in particular, a devastating disease for which there is no cure.