A restricted spectrum of NRAS mutations causes Noonan syndrome

Nat Genet. 2010 Jan;42(1):27-9. doi: 10.1038/ng.497. Epub 2009 Dec 6.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Child
  • Child, Preschool
  • Chlorocebus aethiops
  • DNA Mutational Analysis
  • Female
  • Genes, ras*
  • Humans
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation*
  • Noonan Syndrome / genetics*
  • Noonan Syndrome / metabolism
  • Noonan Syndrome / pathology
  • Phosphorylation
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Transfection
  • Young Adult
  • ras Proteins / chemistry
  • ras Proteins / genetics*

Substances

  • Mitogen-Activated Protein Kinases
  • ras Proteins