A rare case report on novel pathogenic mutation of TSC2 gene explained at molecular level

Tuberous sclerosis is a neurocutaneous genetic syndrome inherited as autosomal dominant pattern. This disease is caused by mutations of either of the tumor suppressor genes named TSC1 or TSC2 gene. It encodes for hamartin and tuberin which modulates mTOR pathway and regulate cell growth and proliferation. We report a case of a 7 year old child positive for pathogenic variant of TSC2 mutation having multiple seizures, angiofibromas, shagreen patch. Imaging studies are indicative of multiple calcified nodules in sub ependymal region, abnormal subcortical white matter suggestive of tuberous sclerosis. Molecular tests suggested that the mutation occurred results in alteration of splicing mechanism. Due to such alteration, the incomplete TSC2 gene encodes an altered tuberin protein i.e., unable to interact with Ras homologue enriched in brain (Rheb), leading to dysregulation of mammalian target of rapamycin (mTOR) signalling causing tuberous sclerosis disease.