title: Phenotypes associated with inherited and developmental somatic mutations in genes encoding mTOR pathway components.
abstract: Mutations affecting the genes that encode upstream components in the mammalian (or mechanistic) target of rapamycin signalling pathway are associated with a group of rare inherited and developmental disorders that show overlapping clinical features. These include predisposition to a variety of benign or malignant tumours, localized overgrowth, developmental abnormalities of the brain, neurodevelopmental disorders and epilepsy. Many of these features have been linked to hyperactivation of signalling via mammalian target of rapamycin complex 1, suggesting that inhibitors of this complex such as rapamycin and its derivatives may offer new opportunities for therapy. In this review we describe this group of inherited and developmental disorders and discuss recent progress in their treatment via mTORC1 inhibition.
authors.affiliation: Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. Electronic address: SaxenaA@cf.ac.uk.
authors.forename: Anurag
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Sampson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000068338:Everolimus; D030342:Genetic Diseases, Inborn / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors* / Q000235:genetics*; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D046912:Multiprotein Complexes; D000068338:Everolimus; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Everolimus; Rapamycin; Sirolimus; mTOR; mTORC1; mTORC2