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
  • 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.