The RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway.
Endocr Rev
; 39(5): 676-700, 2018 10 01.
Article
in En
| MEDLINE
| ID: mdl-29924299
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
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Germ-Line Mutation
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Ras Proteins
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Craniofacial Abnormalities
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Mitogen-Activated Protein Kinases
Limits:
Humans
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Male
Language:
En
Journal:
Endocr Rev
Year:
2018
Document type:
Article
Affiliation country:
France
Publication country:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA