Systemic mast cell activation disease: the role of molecular genetic alterations in pathogenesis, heritability and diagnostics

Immunology. 2012 Nov;137(3):197-205. doi: 10.1111/j.1365-2567.2012.03627.x.


Despite increasing understanding of its pathophysiology, the aetiology of systemic mast cell activation disease (MCAD) remains largely unknown. Research has shown that somatic mutations in kinases are necessary for the establishment of a clonal mast cell population, in particular mutations in the tyrosine kinase Kit and in enzymes and receptors with crucial involvement in the regulation of mast cell activity. However, other, as yet undetermined, abnormalities are necessary for the manifestation of clinical disease. The present article reviews molecular genetic research into the identification of disease-associated genes and their mutational alterations. The authors also present novel data on familial systemic MCAD and review the associated literature. Finally, the importance of understanding the molecular basis of inherited mutations in terms of diagnostics and therapy is emphasized.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genetic Predisposition to Disease*
  • Humans
  • Mastocytosis, Systemic / diagnosis
  • Mastocytosis, Systemic / genetics*
  • Mastocytosis, Systemic / immunology
  • Mastocytosis, Systemic / therapy
  • Mutation
  • Polymorphism, Genetic
  • Proto-Oncogene Proteins c-kit / genetics


  • Proto-Oncogene Proteins c-kit