Document Detail


The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation.
MedLine Citation:
PMID:  19467855     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Ras/mitogen activated protein kinase (MAPK) pathway is essential in the regulation of the cell cycle, differentiation, growth and cell senescence, all of which are critical to normal development. It is therefore not surprising that its dysregulation has profound effects on development. A class of developmental syndromes, the 'RASopathies', is caused by germline mutations in genes that encode protein components of the Ras/MAPK pathway. The vast majority of these mutations result in increased signal transduction down the Ras/MAPK pathway, but usually to a lesser extent than somatic mutations associated with oncogenesis. Each syndrome exhibits unique phenotypic features, however, since they all cause dysregulation of the Ras/MAPK pathway, there are numerous overlapping phenotypic features between the syndromes, including characteristic facial features, cardiac defects, cutaneous abnormalities, neurocognitive delay and a predisposition to malignancies. Here we review the clinical and underlying molecular basis for each of these syndromes.
Authors:
William E Tidyman; Katherine A Rauen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2009-05-19
Journal Detail:
Title:  Current opinion in genetics & development     Volume:  19     ISSN:  1879-0380     ISO Abbreviation:  Curr. Opin. Genet. Dev.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-15     Completed Date:  2009-09-25     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  9111375     Medline TA:  Curr Opin Genet Dev     Country:  England    
Other Details:
Languages:  eng     Pagination:  230-6     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Division of Medical Genetics, University of California, San Francisco, CA 94115, USA. William.tidyman@ucsf.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Germ-Line Mutation
Humans
Mitogen-Activated Protein Kinases / genetics,  metabolism*
Models, Biological
Noonan Syndrome / genetics,  pathology,  physiopathology
SOS1 Protein / genetics,  metabolism
Signal Transduction / genetics,  physiology*
Syndrome
ras Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
HD048502/HD/NICHD NIH HHS; K23 HD048502-05/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/SOS1 Protein; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.6.5.2/ras Proteins
Comments/Corrections

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