The RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway
- 1 October 2018
- journal article
- review article
- Published by The Endocrine Society in Endocrine Reviews
- Vol. 39 (5), 676-700
- https://doi.org/10.1210/er.2017-00232
Abstract
Noonan syndrome [NS; Mendelian Inheritance in Men (MIM) #163950] and related syndromes [Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome; MIM #151100), Noonan-like syndrome with loose anagen hair (MIM #607721), Costello syndrome (MIM #218040), cardio-facio-cutaneous syndrome (MIM #115150), type I neurofibromatosis (MIM #162200), and Legius syndrome (MIM #611431)] are a group of related genetic disorders associated with distinctive facial features, cardiopathies, growth and skeletal abnormalities, developmental delay/mental retardation, and tumor predisposition. NS was clinically described more than 50 years ago, and disease genes have been identified throughout the last 3 decades, providing a molecular basis to better understand their physiopathology and identify targets for therapeutic strategies. Most of these genes encode proteins belonging to or regulating the so-called RAS/MAPK signaling pathway, so these syndromes have been gathered under the name RASopathies. In this review, we provide a clinical overview of RASopathies and an update on their genetics. We then focus on the functional and pathophysiological effects of RASopathycausing mutations and discuss therapeutic perspectives and future directions.Funding Information
- Inserm
- H2020 European Research Council (NS-EuroNet)
- DGOS/CHU
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