Mutation Spectrum and Phenotypic Features in Noonan Syndrome with PTPN11 Mutations: Definition of Two Novel Mutations

Indian J Pediatr. 2016 Jun;83(6):517-21. doi: 10.1007/s12098-015-1998-6. Epub 2016 Jan 28.


Objectives: To evaluate the spectrum of PTPN11 gene mutations in Noonan syndrome patients and to study the genotype-phenotype associations.

Methods: In this study, twenty Noonan syndrome patients with PTPN11 mutations were included. The patients underwent a detailed clinical and physical evaluation. To identify inherited cases, parents of all mutation positive patients were analyzed.

Results: Thirteen different PTPN11 mutations, two of them being novel, were detected in the study group. These mutations included eleven missense mutations: p.G60A, p.D61N, p.Y62D, p.Y63C, p.E69Q, p.Q79R, p.Y279C,p.N308D, p.N308S, p.M504V, p.Q510R and two novel missense mutations: p.I56V and p.I282M. The frequency of cardiac abnormalities and short stature were found to be 80 % and 80 %, respectively. Mental retardation was not observed in patients having exon 8 mutations. No significant correlations were detected between other phenotypic features and genotypes.

Conclusions: By identifying genotype-phenotype correlations, this study provides information on phenotypes observed in NS patients with different PTPN11 mutations.

Keywords: Noonan syndrome; PTPN11; Pulmonary stenosis; Rasopathy; Short stature.

MeSH terms

  • Child
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Male
  • Mutation*
  • Noonan Syndrome / genetics*
  • Phenotype
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics*


  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11