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Two responsible genes, <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic>, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin\u2013Tuberin complex is involved in the phosphoinositide 3\u2010kinase\u2013protein kinase\u00a0B\u2013mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex\u00a01 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex\u00a01 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex\u00a01 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, \u201ca cross\u2010sectional medical examination system,\u201d a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex\u2010associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex.<\/jats:p>","DOI":"10.1111\/iju.13390","type":"journal-article","created":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T06:52:39Z","timestamp":1498891959000},"page":"681-691","source":"Crossref","is-referenced-by-count":54,"title":["Tuberous sclerosis complex: Recent advances in manifestations and therapy"],"prefix":"10.1111","volume":"24","author":[{"given":"Mari","family":"Wataya\u2010Kaneda","sequence":"first","affiliation":[{"name":"Department of Dermatology Graduate School of Medicine Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohide","family":"Uemura","sequence":"additional","affiliation":[{"name":"Department of Urology Graduate School of Medicine Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutoshi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Urology Graduate School of Medicine Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Allergy and Rheumatic Diseases Graduate School of Medicine Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Osuga","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology Graduate School of Medicine Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuriko","family":"Kagitani\u2010Shimono","sequence":"additional","affiliation":[{"name":"Department of United Graduate School of Child Development Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Nonomura","sequence":"additional","affiliation":[{"name":"Department of Urology Graduate School of Medicine Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Tuberous Sclerosis Complex Board of Osaka University Hospital","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02247-9"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5327.805"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90618-Z"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02474.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/302381"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-5945-8-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023379"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31803068c7"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201402"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2013.08.001"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb839"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61767-X"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-824X-4-11"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12122"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61134-9"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa063564"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20784"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e31816e22a5"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2006.07.017"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2015.07.018"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.12.053"},{"key":"e_1_2_11_23_1","volume-title":"Traite Theorique et Pratique des Maladies de la Peau","author":"Rayer PFO","year":"1835"},{"key":"e_1_2_11_24_1","first-page":"1","article-title":"Ein Herz von einen Neugeborene welches mehrere thels nach aussen, theils nach den Hohlein prominirende Tumoren(myomata) trug","volume":"20","author":"Recklinghausen F","year":"1862","journal-title":"MonatschrGebrutsheklkd"},{"key":"e_1_2_11_25_1","first-page":"81","article-title":"Sclerose tubereuse des circonvultions cerebrales:idotie et epilepsie hemiplegique","volume":"1","author":"Bourneville DM","year":"1880","journal-title":"Arch. 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