International Journal of Scientific Reports | April 2019 | Vol 5 | Issue 4 Page 107 International Journal of Scientific Reports Dey S et al. Int J Sci Rep. 2019 Apr;5(4):107-111 http://www.sci-rep.com pISSN 2454-2156 | eISSN 2454-2164 Case Report A rare case report on novel pathogenic mutation of TSC2 gene explained at molecular level Shankar Dey 1 , Pritha Chakraborty 2 *, Sunil Kanti Mondal 2 INTRODUCTION Tuberous sclerosis complex (TSC) is a rare neuro- cutaneous syndrome with an autosomal dominant genetic inheritance caused by mutations in two tumor-suppressor genes TSC1 (chr 9q34) or TSC2 (chr16p13.3) gene with the prevalence of one in 6000 live birth, affecting both sexes. 1 TSC is marked primarily by the formation of hamartomas in a wide variety of organs including the brain, heart, lungs, kidneys, and skin which becomes apparent only in late childhood and also associated with neurological manifestations resulting in epilepsy, learning difficulties, behavioural problems, and renal failure, among other complications. 2,3 No molecular link has been established between the genes responsible for the hamartoma syndromes. 4 Loss of heterozygosity of either of the TSC1 and TSC2 or dysregulation of mTOR is an essential causative factor in the disease TSC. Structure associated with tuberous sclerosis complex TSC1 and TSC2 gene encodes for hamartin and tuberin that forms heterodimers and work together to regulate cell growth and size. TBC1D7 is associated with Tuberous Sclerosis Complex as it binds through TSC1 in the absence of TSC2. 5 Loss of TBC1D7 partially disrupts the association between TSC1 and TSC2, resulting in a decrease in Rheb-GAP activity. TSC1 consists of 23 exons, 21 contain coding sequence and two are alternatively spliced. Hamartin protein comprised of 1164 amino acids (130kDa) and had no significant homology to tuberin. The amino acid residues 145–510 of hamartin contain the function for activation of Rho GTPase. TSC2 gene consists of 41 exons of which exon 25, 26 and 31 are subjected to alternative splicing. 6 Tuberin has a ABSTRACT 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. Keywords: Tuberous sclerosis, Neurocutenous, Hamartin, Tuberin, Rapamycin 1 Department of Gynaecology and Obstetrics, ESI Hospital, Asansol, West Bengal, India 2 Department of Biotechnology, The University of Burdwan, Bardhaman, West Bengal, India Received: 14 January 2019 Revised: 27 February 2019 Accepted: 28 February 2019 *Correspondence: Ms. Pritha Chakraborty, E-mail: prithachakraborty895@gmail.com Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: http://dx.doi.org/10.18203/issn.2454-2156.IntJSciRep20191434