Human Molecular Genetics, de Duve Institute, University of Louvain, Brussels, Belgium.
Human Molecular Genetics, de Duve Institute, University of Louvain, Brussels, Belgium; Center for Vascular Anomalies, Division of Plastic Surgery, VASCERN VASCA European Reference Centre, Saint Luc University Hospital, Brussels, Belgium.
Semin Pediatr Surg. 2020 Oct;29(5):150967. doi: 10.1016/j.sempedsurg.2020.150967. Epub 2020 Sep 16.
Vascular anomalies are developmental defects of the vasculature and encompass a variety of disorders. The identification of genes mutated in the different malformations provides insight into the etiopathogenic mechanisms and the specific roles the associated proteins play in vascular development and maintenance. A few familial forms of vascular anomalies exist, but most cases occur sporadically. It is becoming evident that somatic mosaicism plays a major role in the formation of vascular lesions. The use of Next Generating Sequencing for high throughput and "deep" screening of both blood and lesional DNA and RNA has been instrumental in detecting such low frequency somatic changes. The number of novel causative mutations identified for many vascular anomalies has soared within a 10-year period. The discovery of such genes aided in unraveling a holistic overview of the pathogenic mechanisms, by which in vitro and in vivo models could be generated, and opening the doors to development of more effective treatments that do not address just symptoms. Moreover, as many mutations and the implicated signaling pathways are shared with cancers, current oncological therapies could potentially be repurposed for the treatment of vascular anomalies.
血管异常是脉管系统的发育缺陷，包括多种疾病。不同畸形中突变基因的鉴定为发病机制提供了深入了解，也明确了相关蛋白在血管发育和维持中的特定作用。存在一些家族性血管异常形式，但大多数病例是散发性的。越来越明显的是，体细胞嵌合在血管病变的形成中起着主要作用。下一代测序技术用于血液和病变 DNA 和 RNA 的高通量和“深度”筛选，对于检测这种低频体细胞变化非常重要。在 10 年内，许多血管异常的新致病突变的鉴定数量猛增。这些基因的发现有助于揭示发病机制的整体概况，从而可以生成体外和体内模型，并为开发更有效的治疗方法开辟道路，这些方法不仅可以解决症状。此外，由于许多突变和涉及的信号通路与癌症共享，当前的肿瘤治疗方法可能会被重新用于治疗血管异常。
