Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy

@article{Pandit2007GainoffunctionRM,
  title={Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy},
  author={Bhaswati Pandit and Anna Sarkozy and Len A. Pennacchio and Claudio Carta and Kimihiko Oishi and Simone Martinelli and Edgar A Pogna and Wendy S. Schackwitz and Anna Ustaszewska and Andrew P. Landstrom and J. Martijn Bos and Steve Ommen and Giorgia Esposito and Francesca Romana Lepri and Christian Faul and Peter Mundel and Juan Pedro L{\'o}pez Siguero and Romano Tenconi and Angelo Selicorni and Cesare Rossi and Laura Mazzanti and Isabella Torrente and Bruno Marino and Maria Cristina Digilio and Giuseppe Zampino and Michael J. Ackerman and Bruno Dallapiccola and Marco Tartaglia and Bruce D. Gelb},
  journal={Nature Genetics},
  year={2007},
  volume={39},
  pages={1007-1012}
}
Noonan and LEOPARD syndromes are developmental disorders with overlapping features, including cardiac abnormalities, short stature and facial dysmorphia. Increased RAS signaling owing to PTPN11, SOS1 and KRAS mutations causes ∼60% of Noonan syndrome cases, and PTPN11 mutations cause 90% of LEOPARD syndrome cases. Here, we report that 18 of 231 individuals with Noonan syndrome without known mutations (corresponding to 3% of all affected individuals) and two of six individuals with LEOPARD… 
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TLDR
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TLDR
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TLDR
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TLDR
A more severe or atypical phenotype was not observed in a patient with Noonan syndrome presenting mutations in two genes of RAS/MAPK pathway, suggesting that these mutations do not exhibit an additive effect.
Activating MRAS mutations cause Noonan syndrome associated with hypertrophic cardiomyopathy.
The RASopathies are a group of genetic syndromes caused by upregulated RAS signaling. Noonan syndrome (NS), the most common entity among the RASopathies, is characterized mainly by short stature,
Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: Molecular diversity and associated phenotypic spectrum
TLDR
To investigate the phenotypic spectrum and molecular diversity of germline mutations affecting BRAF, subjects with a diagnosis of NS, LS, and CFCS were screened for the entire coding sequence of the gene.
PTPN11-associated mutations in the heart: has LEOPARD changed Its RASpots?
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