Gomez MR (1999) Definition and criteria for diagnosis 3ed. Oxford University Press, New York, NY, USA, pp 10–23

Google Scholar 

Mizuguchi M, Ohsawa M, Kashii H, Sato A (2021) Brain symptoms of Tuberous Sclerosis Complex: Pathogenesis and Treatment. Int J Mol Sci 22. https://doi.org/10.3390/ijms22136677

Au KS, Hebert AA, Roach ES, Northrup H (1999) Complete inactivation of the TSC2 gene leads to formation of hamartomas. Am J Hum Genet 65:1790–1795. https://doi.org/10.1086/302648

Article  PubMed  PubMed Central  CAS  Google Scholar 

Green AJ, Smith M, Yates JR (1994) Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients. Nat Genet 6:193–196. https://doi.org/10.1038/ng0294-193

Article  PubMed  CAS  Google Scholar 

Lozovaya N, Gataullina S, Tsintsadze T, Tsintsadze V, Pallesi-Pocachard E, Minlebaev M et al (2014) Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model. Nat Commun 5:4563. https://doi.org/10.1038/ncomms5563

Article  PubMed  CAS  Google Scholar 

Lee JS, Lim BC, Chae JH, Hwang YS, Seong MW, Park SS, Kim KJ (2014) Mutational analysis of paediatric patients with tuberous sclerosis complex in Korea: genotype and epilepsy. Epileptic Disord 16:449–455. https://doi.org/10.1684/epd.2014.0712

Article  PubMed  Google Scholar 

Jang MA, Hong SB, Lee JH, Lee MH, Chung MP, Shin HJ et al (2012) Identification of TSC1 and TSC2 mutations in Korean patients with tuberous sclerosis complex. Pediatr Neurol 46:222–224. https://doi.org/10.1016/j.pediatrneurol.2012.02.002

Article  PubMed  Google Scholar 

Choi JE, Chae JH, Hwang YS, Kim KJ (2006) Mutational analysis of TSC1 and TSC2 in Korean patients with tuberous sclerosis complex. Brain Dev 28:440–446. https://doi.org/10.1016/j.braindev.2006.01.006

Article  PubMed  Google Scholar 

Northrup H, Aronow ME, Bebin EM, Bissler J, Darling TN, de Vries PJ et al (2021) Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management recommendations. Pediatr Neurol 123:50–66. https://doi.org/10.1016/j.pediatrneurol.2021.07.011

Article  PubMed  Google Scholar 

Kim SH, Kim B, Lee JS, Kim HD, Choi JR, Lee ST, Kang HC (2019) Proband-only clinical exome sequencing for neurodevelopmental disabilities. Pediatr Neurol 99:47–54. https://doi.org/10.1016/j.pediatrneurol.2019.02.017

Article  PubMed  Google Scholar 

Rim JH, Kim SH, Hwang IS, Kwon SS, Kim J, Kim HW et al (2018) Efficient strategy for the molecular diagnosis of intractable early-onset epilepsy using targeted gene sequencing. BMC Med Genomics 11:6. https://doi.org/10.1186/s12920-018-0320-7

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ryu S, Kang HC, Lee SC, Byeon SH, Kim SS, Lee CS (2023) Refractive errors, retinal findings, and genotype of Tuberous Sclerosis Complex: a retrospective cohort study. Yonsei Med J 64:133–138. https://doi.org/10.3349/ymj.2022.0451

Article  PubMed  PubMed Central  CAS  Google Scholar 

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424. https://doi.org/10.1038/gim.2015.30

Article  PubMed  PubMed Central  Google Scholar 

Nellist M, van Slegtenhorst MA, Goedbloed M, van den Ouweland AM, Halley DJ, van der Sluijs P (1999) Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin. J Biol Chem 274:35647–35652. https://doi.org/10.1074/jbc.274.50.35647

Article  PubMed  CAS  Google Scholar 

van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A et al (1998) Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet 7:1053–1057. https://doi.org/10.1093/hmg/7.6.1053

Article  PubMed  Google Scholar 

Consortium TU (2022) UniProt: the Universal protein knowledgebase in 2023. Nucleic Acids Res 51:D523–D531. https://doi.org/10.1093/nar/gkac1052

Article  CAS  Google Scholar 

Ding Y, Zhou Y, Yu L, Zhang L, Zhou S, Wang Y, Wang J (2021) Correlation between epilepsy and genotype: a large retrospective tuberous sclerosis complex cohort. Seizure 91:273–277. https://doi.org/10.1016/j.seizure.2021.06.036

Article  PubMed  Google Scholar 

Au KS, Williams AT, Roach ES, Batchelor L, Sparagana SP, Delgado MR et al (2007) Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med 9:88–100. https://doi.org/10.1097/gim.0b013e31803068c7

Article  PubMed  CAS  Google Scholar 

Sancak O, Nellist M, Goedbloed M, Elfferich P, Wouters C, Maat-Kievit A et al (2005) Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype–phenotype correlations and comparison of diagnostic DNA techniques in tuberous sclerosis complex. Eur J Hum Genet 13:731–741

Article  PubMed  CAS  Google Scholar 

Suspitsin EN, Yanus GA, Dorofeeva MY, Ledashcheva TA, Nikitina NV, Buyanova GV et al (2018) Pattern of TSC1 and TSC2 germline mutations in Russian patients with tuberous sclerosis. J Hum Genet 63:597–604. https://doi.org/10.1038/s10038-018-0416-0

Article  PubMed  CAS  Google Scholar 

Kingswood JC, d’Augeres GB, Belousova E, Ferreira JC, Carter T, Castellana R et al (2017) TuberOus SClerosis registry to increase disease awareness (TOSCA) - baseline data on 2093 patients. Orphanet J Rare Dis 12:2. https://doi.org/10.1186/s13023-016-0553-5

Article  PubMed  PubMed Central  Google Scholar 

Nabbout R, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P et al (2019) Epilepsy in tuberous sclerosis complex: findings from the TOSCA Study. Epilepsia Open 4:73–84. https://doi.org/10.1002/epi4.12286

Article  PubMed  Google Scholar 

Chu-Shore CJ, Major P, Camposano S, Muzykewicz D, Thiele EA (2010) The natural history of epilepsy in tuberous sclerosis complex. Epilepsia 51:1236–1241. https://doi.org/10.1111/j.1528-1167.2009.02474.x

Article  PubMed  Google Scholar 

Curatolo P, Moavero R, de Vries PJ (2015) Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol 14:733–745. https://doi.org/10.1016/S1474-4422(15)00069-1

Article  PubMed  Google Scholar 

Togi S, Ura H, Hatanaka H, Niida Y (2022) Genotype and phenotype Landscape of 283 Japanese patients with tuberous sclerosis complex. Int J Mol Sci 23. https://doi.org/10.3390/ijms231911175

Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J et al (2001) Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet 68:64–80

Article  PubMed  CAS  Google Scholar 

Sancak O, Nellist M, Goedbloed M, Elfferich P, Wouters C, Maat-Kievit A et al (2005) Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype–phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex. Eur J Hum Genet 13:731–741. https://doi.org/10.1038/sj.ejhg.5201402

Article  PubMed  CAS  Google Scholar 

Kothare SV, Singh K, Chalifoux JR, Staley BA, Weiner HL, Menzer K, Devinsky O (2014) Severity of manifestations in tuberous sclerosis complex in relation to genotype. Epilepsia 55:1025–1029. https://doi.org/10.1111/epi.12680

Article  PubMed  CAS  Google Scholar 

Jansen F, Braams O, Vincken K, Algra A, Anbeek P, Jennekens-Schinkel A et al (2008) Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations. Neurology 70:908–915

Article  PubMed  CAS  Google Scholar 

Peron A, Vignoli A, Briola F, Morenghi E, Tansini L, Alfano RM et al (2018) Deep phenotyping of patients with tuberous sclerosis complex and no mutation identified in TSC1 and TSC2. Eur J Med Genet 61:403–410. https://doi.org/10.1016/j.ejmg.2018.02.005

Article  PubMed  Google Scholar 

Ogorek B, Hamieh L, Hulshof HM, Lasseter K, Klonowska K, Kuijf H et al (2020) TSC2 pathogenic variants are predictive of severe clinical manifestations in TSC infants: results of the EPISTOP study. Genet Med 22:1489–1497. https://doi.org/10.1038/s41436-020-0823-4