Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome

@article{Tartaglia2001MutationsIP,
  title={Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome},
  author={Marco Tartaglia and Ernest L. Mehler and Rosalie Goldberg and Giuseppe Zampino and Han G. Brunner and Hannie Kremer and Ineke van der Burgt and Andrew H Crosby and Andra Ion and Steve Jeffery and Kamini Kalidas and Michael A. Patton and Raju Kucherlapati and Bruce D. Gelb},
  journal={Nature Genetics},
  year={2001},
  volume={29},
  pages={465-468}
}
Noonan syndrome (MIM 163950) is an autosomal dominant disorder characterized by dysmorphic facial features, proportionate short stature and heart disease (most commonly pulmonic stenosis and hypertrophic cardiomyopathy). Webbed neck, chest deformity, cryptorchidism, mental retardation and bleeding diatheses also are frequently associated with this disease. This syndrome is relatively common, with an estimated incidence of 1 in 1,000–2,500 live births. It has been mapped to a 5-cM region (N-SH2… 
Mutation N308T of protein tyrosine phosphatase SHP-2 in two Senegalese patients with Noonan syndrome
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This study identified in two patients, a c.923A˃C mutation in exon 8, predicting Asn308Thr (N308T) on SHP-2 protein, the first time that this mutation is described in Noonan syndrome in Africa, while codon 308 was reported as a hot spot mutation site in other populations.
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TLDR
The spectrum and distribution of PTPN11 mutations in a large, well-characterized cohort with NS revealed that pulmonic stenosis was more prevalent among the group of subjects with NS who had PTP N11 mutations than it was in the group without them, andotype-phenotype analysis revealed that hypertrophic cardiomyopathy was less prevalent among those with PTPn11 mutations.
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A new mutation in the C-SH2 domain of PTPN11 causes Noonan syndrome with multiple giant cell lesions
TLDR
It is demonstrated for the first time that a unique mutation affecting this, otherwise unaffected signaling route, can cause both NS and NS/MGCL in the same family and confirms that NS/ MGCL is not a distinct entity but rather that MGCL represents a rare complication of NS.
PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) mutations in seven Japanese patients with Noonan syndrome.
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The results provide further support to the notion that PTPN11 mutations are responsible for the development of Noonan syndrome in a substantial fraction of patients and that relatively infrequent features ofnoonan syndrome, such as sensory deafness and bleeding diathesis, can also result from mutations of PTPn11.
Two novel and one recurrent PTPN11 mutations in LEOPARD syndrome
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Two novel and one recurrent PTPN11 mutations identified in LS patients are reported, both of which are novel and recurrent.
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