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


  • Shankar Dey Department of Gynaecology and Obstetrics, ESI Hospital, Asansol, West Bengal
  • Pritha Chakraborty Department of Biotechnology, The University of Burdwan, Bardhaman, West Bengal
  • Sunil Kanti Mondal Department of Biotechnology, The University of Burdwan, Bardhaman, West Bengal




Tuberous sclerosis, Neurocutenous, Hamartin, Tuberin, Rapamycin


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.


Metrics Loading ...


Leung AKC, Robson LM. Tuberous Sclerosis Complex: A Review. J Pediatr Health Care. 2007;21(2):108-14.

Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006;355:1345–56.

Curatolo P, Maria BL. Tuberous sclerosis. In: Dulac O, Lassonade M, Sarnat HB, editors. Pediatric Neurology part I. Elsevier B.V; Handbooks of Clinical Neurology; 2013: 323-331.

Inoki K, Corradetti MN, Guan KL. Dysregulation of the TSC-mTOR pathway in human disease. Nature Genetics. 2005;37(1):19–24.

Rosner M, Hanneder M, Siegel N, Valli A, Hengstschlager M. The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners. Mutat Res. 2008;658:234–46.

Cheadle JP, Reeve MP, Sampson JR, Kwiatkowski DJ. Molecular genetic advances in tuberous sclerosis. Hum Genet. 2000;107:97-114.

Manning BD, Cantley LC. Rheb fills a GAP between TSC and TOR. Trends Biochem Sci. 2003;28:573-6.

Ganley IG, du-H L, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem. 2009;284:12297-305.

Maquat LE. Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat Rev Mol Cell Biol. 2004;5(2):89-99.

Chen W, Moore MJ. Spliceosomes. Current Biol. 2015;25(5):181-3.






Case Reports