{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:12:50Z","timestamp":1791112370848,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T00:00:00Z","timestamp":1377561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tuberous sclerosis complex (<jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>) is caused by a mutation in the <jats:styled-content style=\"fixed-case\">TSC1<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">TSC2<\/jats:styled-content> genes. However, 15% of patients have no mutation identified. Tubers and subependymal nodules (<jats:styled-content style=\"fixed-case\">SENs<\/jats:styled-content>) are the typical brain lesions in <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content> and are present in 90\u201395% of patients. The objective of this study is to characterize the specific genotype\u2013phenotype of patients without these lesions. We analyzed the features of 11 patients without typical <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content> neuroanatomic features. Ten had <jats:styled-content style=\"fixed-case\">TSC1<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">TSC2<\/jats:styled-content> mutational analysis, which was negative. Clinically they had lesions thought to be of neural crest (<jats:styled-content style=\"fixed-case\">NC<\/jats:styled-content>) origin, such as hypomelanotic macules, facial angiofibromas, cardiac rhabdomyomas, angiomyolipomas, and lymphangioleiomyomatosis. We hypothesize that patients without tubers and <jats:styled-content style=\"fixed-case\">SENs<\/jats:styled-content> reflect mosaicism caused by a mutation in <jats:styled-content style=\"fixed-case\">TSC1<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">TSC2<\/jats:styled-content> in a <jats:styled-content style=\"fixed-case\">NC<\/jats:styled-content> cell during embryonic development. This may explain the negative results in <jats:styled-content style=\"fixed-case\">TSC1<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TSC2<\/jats:styled-content> testing in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> from peripheral leukocytes.<\/jats:p>","DOI":"10.1111\/cge.12245","type":"journal-article","created":{"date-parts":[[2013,7,31]],"date-time":"2013-07-31T19:43:25Z","timestamp":1375299805000},"page":"149-154","source":"Crossref","is-referenced-by-count":22,"title":["Tuberous sclerosis complex without tubers and subependymal nodules: a phenotype\u2013genotype study"],"prefix":"10.1111","volume":"86","author":[{"given":"S.","family":"Boronat","sequence":"first","affiliation":[{"name":"Department of Neurology Herscot Center for TSC, Massachusetts General Hospital Boston MA USA"},{"name":"Department of Pediatric Neurology Vall d' Hebron Hospital, Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.A.","family":"Shaaya","sequence":"additional","affiliation":[{"name":"Department of Neurology Herscot Center for TSC, Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.M.","family":"Doherty","sequence":"additional","affiliation":[{"name":"Department of Neurology Herscot Center for TSC, Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Caruso","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology Massachusetts General Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.A.","family":"Thiele","sequence":"additional","affiliation":[{"name":"Department of Neurology Herscot Center for TSC, Massachusetts General Hospital Boston MA 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