PTPN11-associated mutations in the heart: has LEOPARD changed Its RASpots?

Trends Cardiovasc Med. 2011 May;21(4):97-104. doi: 10.1016/j.tcm.2012.03.006.


In this review, we focus on elucidating the cardiac function of germline mutations in the PTPN11 gene, encoding the Src homology-2 (SH2) domain-containing protein tyrosine phosphatase SHP2. PTPN11 mutations cause LEOPARD syndrome (LS) and Noonan syndrome (NS), two disorders that are part of a newly classified family of autosomal dominant syndromes termed "RASopathies," which are caused by germline mutations in components of the RAS/RAF/MEK/ERK mitogen activating protein kinase pathway. LS and NS mutants have opposing biochemical properties, and yet, in patients, these mutations produce similar cardiac abnormalities. Precisely how LS and NS mutations lead to such similar disease etiology remains largely unknown. Recent complementary in vitro, ex vivo, and in vivo analyses reveal new insights into the functions of SHP2 in normal and pathological cardiac development. These findings also reveal the need for individualized therapeutic approaches in the treatment of patients with LS and NS and, more broadly, patients with the other "RASopathy" gene mutations as well.

Publication types

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

MeSH terms

  • Animals
  • Cardiomegaly / genetics
  • Disease Models, Animal
  • Genes, ras / genetics
  • Germ-Line Mutation / genetics*
  • Heart Defects, Congenital / genetics*
  • Humans
  • LEOPARD Syndrome / genetics*
  • LEOPARD Syndrome / therapy
  • MAP Kinase Signaling System / genetics
  • Noonan Syndrome / genetics*
  • Noonan Syndrome / therapy
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics*


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