Disorders of brain overgrowth can cause intractable epilepsy, intellectual disability, and autism. They are caused by mutations that activate the RTK-PI3K-AKT signalling cascade in the brain, which regulates the mTOR pathway. At ENCORE we focus in particular on M-CAP Syndrome (Megalencephaly capillary malformation syndrome) which is caused by mutations in the PIK3CA gene, MPPH Syndrome (Megalencephaly, polymicrogyria, polydactyly syndrome) which is caused by mutations in the AKT3 gene, CCND2 gene or the PIK3R2 gene, Smith-Kingsmore syndrome which is caused by mutations in the mTOR gene, and Megalencephaly is caused by mutations in the STRADA/LYK5, PP2A subunits (PPP2R5B, PPP2R5C, PPP2R5D) and RHEB.
Brain overgrowth research at ENCORE is primarily focusing on the role of the PI3K-AKT-mTOR signalling in the brain. For that we use both mouse models (TSC, RHEB) as well as in utero electroporation of mice.
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