Document Detail


A restricted spectrum of NRAS mutations causes Noonan syndrome.
MedLine Citation:
PMID:  19966803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Noonan syndrome, a developmental disorder characterized by congenital heart defects, reduced growth, facial dysmorphism and variable cognitive deficits, is caused by constitutional dysregulation of the RAS-MAPK signaling pathway. Here we report that germline NRAS mutations conferring enhanced stimulus-dependent MAPK activation account for some cases of this disorder. These findings provide evidence for an obligate dependency on proper NRAS function in human development and growth.
Authors:
Ion C Cirstea; Kerstin Kutsche; Radovan Dvorsky; Lothar Gremer; Claudio Carta; Denise Horn; Amy E Roberts; Francesca Lepri; Torsten Merbitz-Zahradnik; Rainer König; Christian P Kratz; Francesca Pantaleoni; Maria L Dentici; Victoria A Joshi; Raju S Kucherlapati; Laura Mazzanti; Stefan Mundlos; Michael A Patton; Margherita Cirillo Silengo; Cesare Rossi; Giuseppe Zampino; Cristina Digilio; Liborio Stuppia; Eva Seemanova; Len A Pennacchio; Bruce D Gelb; Bruno Dallapiccola; Alfred Wittinghofer; Mohammad R Ahmadian; Marco Tartaglia; Martin Zenker
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-06
Journal Detail:
Title:  Nature genetics     Volume:  42     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-28     Completed Date:  2010-02-12     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  27-9     Citation Subset:  IM    
Affiliation:
Institute of Biochemistry and Molecular Biology II, Heinrich-Heine University Medical Center, Düsseldorf, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Amino Acid Sequence
Animals
Base Sequence
COS Cells
Cercopithecus aethiops
Child
Child, Preschool
DNA Mutational Analysis
Female
Genes, ras*
Humans
Male
Middle Aged
Mitogen-Activated Protein Kinases / metabolism
Models, Molecular
Molecular Sequence Data
Mutation*
Noonan Syndrome / genetics*,  metabolism,  pathology
Phosphorylation
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Transfection
Young Adult
ras Proteins / chemistry,  genetics*
Grant Support
ID/Acronym/Agency:
GGP07115//Telethon; ZIA CP010144-12/CP/NCI NIH HHS
Chemical
Reg. No./Substance:
EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.6.5.2/ras Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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