Mutations in components of the hedgehog pathway keep it turned on all the time".
Mutations in components of the lectin pathway have been previously implicated in 3MC syndrome9,10.
Lee, J. H. et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly.
CCMs arise from loss-of-function mutations in components of a complex that negatively regulates MEKK3 KLF2/4 signalling and Rho/ROCK signalling in brain endothelial cells.
Germ-line mutations in components of the Ras/MAPK pathway result in developmental disorders called RASopathies, affecting about 1/1,000 human births.
Mutations in components of the mTOR pathway lead to syndromic neurodevelopmental disroders including TSC, which are often associated with ASD, epilepsy, and intellectual disability.
It is now known that activating point mutations in components of the mitogen-activated protein kinase pathway commonly occur in melanoma.
"The question we were trying to understand is, how is it that when all cells in the body need ribosomes to function, mutations in components that are required for making the ribosomes lead to craniofacial disorders?
Our goal is to understand how different aspects of RNA metabolism are controlled to generate structure and function during development, as well as how mutations in components of the RNA metabolic program lead to congenital disorders and cancer.
Given the large body of evidence implying mTOR function in key aspects of brain development, it is not surprising that hyperactivating, somatic, and germline mutations in components of the PI3K-AKT3-mTOR pathway have been linked with rare ID syndromes associated with (hemi megalencephaly, focal cortical dysplasia, and epilepsy38,39,40,41.
For instance, in budding yeast, mutations in components of the ORC complex affect transcriptional silencing (Foss et al., 1993; Bell et al., 1995; Fox et al., 1995).
