Noonan syndrome and related disorders: genetics and pathogenesis

Annu Rev Genomics Hum Genet. 2005;6:45-68. doi: 10.1146/annurev.genom.6.080604.162305.

Abstract

Noonan syndrome is a pleiomorphic autosomal dominant disorder with short stature, facial dysmorphia, webbed neck, and heart defects. In the past decade, progress has been made in elucidating the pathogenesis of this disorder using a positional cloning approach. Noonan syndrome is now known to be a genetically heterogeneous disorder with nearly one half of cases caused by gain-of-function mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP-2. Similar germ line mutations cause two related genetic disorders, Noonan-like disorder with multiple giant cell lesion syndrome and LEOPARD syndrome, and somatic PTPN11 mutations can underlie certain pediatric hematopoietic malignancies, including juvenile myelomonocytic, acute lymphoblastic, and acute myelogenous leukemias. A mouse model of PTPN11-related Noonan syndrome was recently generated, providing a reagent for studying disease pathogenesis in greater depth as well as experimenting with novel therapeutic strategies.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Female
  • Genetic Linkage
  • Genotype
  • History, 19th Century
  • History, 20th Century
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology
  • Leukemia / genetics
  • Male
  • Mice
  • Models, Molecular
  • Mutation
  • Noonan Syndrome / diagnosis
  • Noonan Syndrome / etiology
  • Noonan Syndrome / genetics*
  • Noonan Syndrome / history
  • Paternal Age
  • Phenotype
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases / chemistry
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / physiology

Substances

  • Intracellular Signaling Peptides and Proteins
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse