{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T21:39:37Z","timestamp":1773092377744,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T00:00:00Z","timestamp":1538006400000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH5T32GM007454"],"award-info":[{"award-number":["NIH5T32GM007454"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["BWF CAMS 1014700"],"award-info":[{"award-number":["BWF CAMS 1014700"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by hamartomatous growths in the brain, kidneys, lungs, skin, heart, and retina. TSC is caused by loss of function mutations in one of two tumor suppressor genes, <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic>. Two\u2010thirds of individuals with TSC have de novo mutations, and individuals with postzygotic pathogenic variants in both <jats:italic>TSC1<\/jats:italic> and <jats:italic>TSC2<\/jats:italic> have been reported. The development of sensitive molecular methods, such as next generation sequencing, has led to an increased ability to detect low\u2010level mosaic variants, which are typically thought to have milder phenotypes because a smaller fraction of cells in the body harbor the mutation. Here, we describe two patients with TSC who had severe phenotypic involvement, but only low\u2010level mosaicism in <jats:italic>TSC2<\/jats:italic>. Given this apparent discrepancy and concern about a missed constitutional variant, we sampled multiple tissues in both cases to confirm these mosaic mutations. Sampling of multiple tissues can be crucial in molecular diagnosis of mosaic TSC. These cases highlight, in general, challenges in molecular diagnosis of genetic conditions due to postzygotic mutations.<\/jats:p>","DOI":"10.1002\/ajmg.c.31656","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T14:01:53Z","timestamp":1538056913000},"page":"374-378","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Minimal mosaicism, maximal phenotype: Discordance between clinical and molecular findings in two patients with tuberous sclerosis"],"prefix":"10.1002","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9971-1368","authenticated-orcid":false,"given":"Heather M.","family":"Byers","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Stanford University School of Medicine  Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana M.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Center for Developmental Biology and Regenerative Medicine Seattle Children's Research Institute  Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian A.","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetic Medicine University of Washington School of Medicine  Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2843-5594","authenticated-orcid":false,"given":"James T.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Center for Developmental Biology and Regenerative Medicine Seattle Children's Research Institute  Seattle Washington"},{"name":"Department of Pediatrics, Division of Genetic Medicine University of Washington School of Medicine  Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31803068c7"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2015.03.013"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2015.10.002"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/316951"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00204934"},{"issue":"4","key":"e_1_2_5_7_1","first-page":"355","article-title":"Review and hypotheses: Somatic mosaicism: Observations related to clinical genetics","volume":"43","author":"Hall J. 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