Germline gain-of-function mutations in SOS1 cause Noonan syndrome

@article{Roberts2007GermlineGM,
  title={Germline gain-of-function mutations in SOS1 cause Noonan syndrome},
  author={Amy E. Roberts and Toshiyuki Araki and Kenneth D. Swanson and Kate T. Montgomery and Taryn A. Schiripo and Victoria A. Joshi and Li Li and Yosuf A. Yassin and Alex M. Tamburino and Benjamin G. Neel and Raju Kucherlapati},
  journal={Nature Genetics},
  year={2007},
  volume={39},
  pages={70-74}
}
Noonan syndrome, the most common single-gene cause of congenital heart disease, is characterized by short stature, characteristic facies, learning problems and leukemia predisposition. Gain-of-function mutations in PTPN11, encoding the tyrosine phosphatase SHP2, cause ∼50% of Noonan syndrome cases. SHP2 is required for RAS-ERK MAP kinase (MAPK) cascade activation, and Noonan syndrome mutants enhance ERK activation ex vivo and in mice. KRAS mutations account for <5% of cases of Noonan syndrome… 
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TLDR
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