Molecular Genetics of the PI3K-AKT-mTOR Pathway in Genodermatoses: Diagnostic Implications and Treatment Opportunities

J Invest Dermatol. 2016 Jan;136(1):15-23. doi: 10.1038/JID.2015.331.

Abstract

A number of critical signaling pathways are required for homeostatic regulation of cell survival, differentiation, and proliferation during organogenesis. One of them is the PI3K-AKT-mTOR pathway consisting of a cascade of inhibitor/activator molecules. Recently, a number of heritable diseases with skin involvement, manifesting particularly with tissue overgrowth, have been shown to result from mutations in the genes in the PI3K-AKT-mTOR and interacting intracellular pathways. Many of these conditions represent an overlapping spectrum of phenotypic manifestations forming a basis for novel, unifying classifications. Identification of the mutant genes and specific mutations in these patients has implications for diagnostics and genetic counseling and provides a rational basis for the development of novel treatment modalities for this currently intractable group of disorders.

Publication types

  • Review

MeSH terms

  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Molecular Biology / methods
  • Molecular Targeted Therapy / methods
  • Mutation / genetics
  • Organogenesis / physiology
  • Phosphatidylinositol 3-Kinases / genetics*
  • Signal Transduction
  • Skin / embryology*
  • Skin Diseases / diagnosis
  • Skin Diseases / genetics*
  • Skin Diseases / therapy
  • TOR Serine-Threonine Kinases / genetics*

Substances

  • MTOR protein, human
  • TOR Serine-Threonine Kinases