2. Academic Validation
  3. A restricted spectrum of NRAS mutations causes Noonan syndrome

A restricted spectrum of NRAS mutations causes Noonan syndrome

  • Nat Genet. 2010 Jan;42(1):27-9. doi: 10.1038/ng.497.
Ion C Cirstea 1,  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
Affiliations

Affiliation

  • 1 Institute of Biochemistry and Molecular Biology II, Heinrich-Heine University Medical Center, Düsseldorf, Germany.
PMID: 19966803 DOI: 10.1038/ng.497
Abstract

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.

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