Department of Pediatrics, Division of Genomic Medicine, University of California Davis, Sacramento, CA 95817, USA.
Department of Pediatrics, UC Davis MIND Institute, Sacramento, CA 95817, USA.
Dis Model Mech. 2022 Feb 1;15(2). doi: 10.1242/dmm.049344.
The term RASopathy was originally created to describe a phenotypically similar group of medical genetic syndromes caused by germline pathogenic variants in components of the RAS/mitogen-activated protein kinase (RAS/MAPK) pathway. In defining a RASopathy syndrome, one needs to consider the complex nature of the RAS/MAPK pathway, the numerous genes and regulatory components involved, its crosstalk with other signaling pathways and the phenotypic spectrum among these syndromes. Three main guiding principles to the definition should be considered. First, a RASopathy is a clinical syndrome with overlapping phenotypic features caused by germline pathogenic variants associated with the RAS/MAPK pathway. Second, a RASopathy is caused by multiple pathogenetic mechanisms, all of which lead to a similar outcome of RAS/MAPK pathway activation/dysregulation. Finally, because a RASopathy has dysfunctional germline RAS/MAPK pathway activation/dysregulation, it may, therefore, be amenable to treatment with pathway modulators.
RAS 病这一术语最初是为了描述一组表型相似的医学遗传综合征，这些综合征是由 RAS/丝裂原活化蛋白激酶（RAS/MAPK）通路的种系致病性变异引起的。在定义 RAS 病综合征时，需要考虑 RAS/MAPK 通路的复杂性、涉及的众多基因和调节成分、它与其他信号通路的串扰以及这些综合征之间的表型谱。应考虑三个主要的定义原则。首先，RAS 病是一种临床综合征，具有重叠的表型特征，由与 RAS/MAPK 通路相关的种系致病性变异引起。其次，RAS 病是由多种致病机制引起的，所有这些机制都导致 RAS/MAPK 通路激活/失调的相似结果。最后，由于 RAS 病的种系 RAS/MAPK 通路激活/失调功能障碍，因此它可能对通路调节剂的治疗有效。
