Noonan syndrome and related disorders: Genetics and pathogenesis

Marco Tartaglia, Bruce D. Gelb

Research output: Contribution to journalArticlepeer-review


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 pediatrie 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.

Original languageEnglish
Pages (from-to)45-68
Number of pages24
JournalAnnual Review of Genomics and Human Genetics
Publication statusPublished - 2005


  • PTPN11
  • SHP-2
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Genetics(clinical)


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