SCIENTIFIC BACKGROUND

BRAF, PTPN11, RAF1

Category:

Scientific Background

LEOPARD syndrome (LS) or cardiomyopathic lentiginosis is a rare, autosomal dominant inherited disorder first documented by Gorlin in 1969. LEOPARD is an acronym for the characteristic clinical symptoms

 

  • lentigines (multiple)
  • electrocardiographic abnormalities
  • ocular hypertelorism
  • pulmonary stenosis
  • abnormal genitals
  • retarded growth
  • deafness

 

In 2002, pathogenic variants in the PTPN11 gene were identified as the molecular cause of LEOPARD syndrome, as was already the case with the partially clinically overlapping Noonan syndrome. Pathogenic variants in the PTPN11 gene can be detected in about 90% of all LS patients, leading exclusively to amino acid exchanges. In contrast to Noonan syndrome, recurring specific PTPN11 amino acid exchanges occur, which lead to loss of the catalytic activity of the non-receptor protein tyrosine phosphatase SHP-2. Pathogenic variants in the proto-oncogenes RAF1 and BRAF have been identified in <5% of LS patients. In less than 5% of patients, no genetic cause has so far been found, although variants in further genes of the RAS-ERK-MAP kinase signal transduction are suspected.

 

References

Ghosh et al. 2015, Dermatol Online J.;21(10) / Carcavilla et al. 2013 Rev Esp Cardiol 66:350 / Sarkozy et al. 2009, Hum Mutat 30:695 / Sarkozy et al. 2008, Orphanet J Rare Dis 3:13 / Pandit et al. 2007, Nat Genet 39:1007 / Kontaridis et al. 2006, J Biol Chem 281:6785 / Tartaglia et al. 2006, Am J Hum Genet 78:279 / Sarkozy et al. 2004, J Med Genet 41:e68 / Digilio et al. 2002, Am J Hum Genet 71:389 / Legius et al. 2002, J Med Genet 39:571 / Gorlin et al. 1969, Am J Dis Child 117:652

GENES

BRAF, PTPN11, RAF1

ASSOCIATED TESTS

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