title: Molecular Genetics of the PI3K-AKT-mTOR Pathway in Genodermatoses: Diagnostic Implications and Treatment Opportunities.
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.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Biotechnology Research Center, Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Vahidnezhad
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Yousseﬁan
authors.affiliation: Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address: Jouni.Uitto@jefferson.edu.
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008967:Molecular Biology / Q000379:methods; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation / Q000235:genetics; D038081:Organogenesis / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D015398:Signal Transduction; D012867:Skin / Q000196:embryology*; D012871:Skin Diseases / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human