Characterization of cellular morphological alterations related to TSC pathogenic variants

Description

Scientific context

Tuberous Sclerosis complex (TSC) is a rare, autosomal dominant, multisystemic disease characterized by the development of tumors in various organs, most commonly affecting the skin, brain, kidneys, lungs, eyes and heart, and it is frequently associated with neuropsychiatric disorders (Winden et al. ). The disease results from pathogenic variants in the or TSC2 genes, which act as regulators of the mTOR pathway. Loss of function of the TSC complex induces constitutive activation of mTORC1, leading to metabolic reprogramming involving mitochondria. Although the disease is multisystemic and phenotypic variability can be considerable, severe epilepsy occurs in 70–90% of affected individuals and is responsible for major morbidity and neuropsychiatric complications. Moreover, despite advances in epilepsy treatment, about 40% of TSC patients present with refractory epilepsy, with limited therapeutic options to handle this ki...