Clinical and molecular characterization of 40 patients with Noonan syndrome

Eur J Med Genet. Nov-Dec 2008;51(6):566-72. doi: 10.1016/j.ejmg.2008.06.011. Epub 2008 Jul 17.

Abstract

Noonan syndrome (NS, OMIM 163950) is an autosomal dominant disorder, with a prevalence at birth of 1:1000-1:2500 live births, characterized by short stature, facial and skeletal dysmorphisms, cardiovascular defects and haematological anomalies. Missense mutations of PTPN11 gene account for approximately 50% of NS cases, while molecular lesions of other genes of the RAS/MAPK pathway -KRAS, SOS1 and RAF1 - play a minor role in the molecular pathogenesis of the disease. Forty patients were enrolled in the study with a PTPN11 mutation detection rate of 31.5%, including a novel missense mutation, Phe285Ile, in a familial case with high intrafamilial phenotypic variability. All patients negative for PTPN11 mutations were further screened for mutations of the KRAS, SOS1, and RAF1 genes, revealing a Thr266Lys substitution in SOS1 in a single patient, a newborn with a subtle phenotype, characterized by facial dysmorphisms and a mild pulmonic stenosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Mutation, Missense
  • Noonan Syndrome / genetics*
  • Noonan Syndrome / pathology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics

Substances

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