Nguyen Ha-Long, Boon Laurence M, Vikkula Miikka
Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
Center for Vascular Anomalies, Division of Plastic Surgery, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.
Semin Pediatr Surg. 2014 Aug;23(4):221-6. doi: 10.1053/j.sempedsurg.2014.06.014. Epub 2014 Jun 19.
Vascular anomalies are developmental defects of the vasculature and encompass a variety of disorders. The majority of these occur sporadically, yet a few are reported to be familial. The identification of genes mutated in the different malformations provides insight into their etiopathogenic mechanisms and the specific roles the associated proteins play in vascular development and maintenance. It is becoming evident that somatic mosaicism plays a major role in the formation of vascular lesions. The importance of utilizing Next-Generating Sequencing (NGS) for high-throughput and "deep" screening of both blood and lesional DNA and RNA is thus emphasized, as the somatic changes are present in low quantities. There are several examples where NGS has already accomplished discovering these changes. The identification of all the causative genes and unraveling of a holistic overview of the pathogenic mechanisms should enable generation of in vitro and in vivo models and lead to development of more effective treatments, not only targeted on symptoms.
血管异常是血管的发育缺陷，包括多种病症。其中大多数是散发性的，但也有少数据报道是家族性的。对不同畸形中发生突变的基因进行鉴定，有助于深入了解其发病机制以及相关蛋白质在血管发育和维持中所起的特定作用。越来越明显的是，体细胞镶嵌现象在血管病变的形成中起主要作用。因此，强调了利用新一代测序（NGS）对血液和病变DNA及RNA进行高通量和“深度”筛查的重要性，因为体细胞变化的数量很少。有几个例子表明，NGS已经成功发现了这些变化。鉴定所有致病基因并全面了解致病机制，应该能够建立体外和体内模型，并导致开发出更有效的治疗方法，而不仅仅是针对症状。
