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Endocr Rev. 2018 Oct 1;39(5):676-700. doi: 10.1210/er.2017-00232.

The RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway.

Author information

1
INSERM UMR 1048, Institute of Cardiovascular and Metabolic Diseases (I2MC), University of Toulouse Paul Sabatier, Toulouse, France.
2
Endocrine, Bone Diseases, and Genetics Unit, Children's Hospital, Toulouse University Hospital, Toulouse, France.

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 RASopathy-causing mutations and discuss therapeutic perspectives and future directions.

PMID:
29924299
DOI:
10.1210/er.2017-00232
[Indexed for MEDLINE]

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