{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:35:35Z","timestamp":1791477335803,"version":"4.3.4"},"reference-count":16,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome caused by either <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic> gene mutations. About 15% of TSC patients remain without genetic diagnosis by conventional analysis despite clinical evidence. It is important to identify somatic mosaics, as therapeutic options are now available in patients with <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic> mutations. Here, we describe the clinical and genetic characteristics of four male TSC patients with low\u2010level mosaicism. Patients presented at ages between 9\u00a0months and 32\u2009years. Clinical manifestations varied considerably and included brain lesions in all four patients, cardiac rhabdomyomas in two young patients, skin involvement in two patients, and retinal hamartomas and renal angiomyolipomas in three patients. One patient presented with epileptic seizures and psychomotor delay. Low levels of mosaicism for <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic> mutation were found in different tissue samples employing next generation sequencing and multiple ligation\u2010dependent probe amplification. The five disease\u2010associated variants, including one second\u2010hit mutation, include three truncating mutations and one deletion in <jats:italic>TSC2<\/jats:italic>, and one truncating mutation in <jats:italic>TSC1<\/jats:italic>. Sanger sequencing, allele\u2010specific oligonucleotide PCR (ASO\u2010PCR), and droplet digital PCR were used to confirm and quantify the disclosed mutations. Genetic identification of low\u2010level mosaicism for TSC remains challenging but is important for optimal surveillance and management.<\/jats:p>","DOI":"10.1002\/ajmg.a.62433","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T13:59:29Z","timestamp":1627653569000},"page":"3851-3858","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Low\u2010level mosaicism in tuberous sclerosis complex in four unrelated patients: Comparison of clinical characteristics and diagnostic pathways"],"prefix":"10.1002","volume":"185","author":[{"given":"H\u00e9ctor Hugo","family":"Manzanilla\u2010Romero","sequence":"first","affiliation":[{"name":"Institute of Human Genetics Medical University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisa","family":"Weis","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics, Kepler University Hospital Johannes Kepler University  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Schnaiter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Medical University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-0672","authenticated-orcid":false,"given":"Sabine","family":"Rudnik\u2010Sch\u00f6neborn","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Medical University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31656"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61279-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-4040"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100505"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0562-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.10.009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2017.07.004"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-015-0155-4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20880"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23237"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/514888"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0764-z"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18332"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0520-3"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005637"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt597"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62433","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62433","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62433","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T10:19:50Z","timestamp":1692958790000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,30]]},"references-count":16,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/ajmg.a.62433"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62433","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,30]]},"assertion":[{"value":"2021-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}