{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:31:51Z","timestamp":1786350711864,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":221,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem genetic disorder caused by pathogenic variants in the\n                    <jats:italic>TSC1<\/jats:italic>\n                    or\n                    <jats:italic>TSC2<\/jats:italic>\n                    genes, resulting in dysregulation of the mTOR signaling pathway and subsequent hamartoma formation. Although the genetic basis of TSC is well established, population\u2010specific data on\n                    <jats:italic>TSC1<\/jats:italic>\n                    and\n                    <jats:italic>TSC2<\/jats:italic>\n                    variants are still emerging. The aim of this study was to characterize the variant spectrum of the\n                    <jats:italic>TSC1<\/jats:italic>\n                    and\n                    <jats:italic>TSC2<\/jats:italic>\n                    genes in a cohort of 34 unrelated probands from Greece, 26 of whom had a definite TSC diagnosis, whereas eight had a possible TSC diagnosis. Targeted next\u2010generation sequencing (NGS) was performed to analyze all coding exons and flanking exon\u2013intron boundaries of\n                    <jats:italic>TSC1<\/jats:italic>\n                    and\n                    <jats:italic>TSC2<\/jats:italic>\n                    . Identified variants were subsequently validated by Sanger sequencing. Pathogenic or likely pathogenic variants were identified in 22 of 34 probands, corresponding to an overall diagnostic yield of 65% using the testing strategy applied in this study. Of these variants, 32% (7\/22) occurred in\n                    <jats:italic>TSC1<\/jats:italic>\n                    and 68% (15\/22) in\n                    <jats:italic>TSC2<\/jats:italic>\n                    ; seven variants (7\/22; 32%) were previously unreported. The molecular detection rate was 77% (20\/26) for patients meeting the criteria for definite clinical TSC diagnosis and 25% (2\/8) for those with a possible TSC diagnosis. Exploratory genotype\u2013phenotype analysis revealed a trend toward a more severe clinical presentation among patients harboring\n                    <jats:italic>TSC2<\/jats:italic>\n                    variants. These findings expand the known molecular landscape of TSC and support the clinical utility of genetic testing for diagnosis, genetic counseling, and patient management.\n                  <\/jats:p>","DOI":"10.1155\/humu\/4508699","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T08:15:27Z","timestamp":1786349727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Characterization of\n                    <i>TSC1<\/i>\n                    and\n                    <i>TSC2<\/i>\n                    Variants in a Greek Cohort of Tuberous Sclerosis Complex Patients"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8257-3704","authenticated-orcid":false,"given":"Socratis N.","family":"Avgeris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2751-2332","authenticated-orcid":false,"given":"Florentia","family":"Fostira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9865-0682","authenticated-orcid":false,"given":"Paraskevi","family":"Apostolou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1660-9577","authenticated-orcid":false,"given":"Angeliki","family":"Delimitsou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1210-6859","authenticated-orcid":false,"given":"Stefanos","family":"Smyrniotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7509-3510","authenticated-orcid":false,"given":"Drakoulis","family":"Yannoukakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9535-2134","authenticated-orcid":false,"given":"Dimitrios J.","family":"Stravopodis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9536-8905","authenticated-orcid":false,"given":"Popi","family":"Syntichaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8393-8648","authenticated-orcid":false,"given":"Gerassimos E.","family":"Voutsinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedhc.2006.05.004"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5327.805"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90618-Z"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.06.009"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00506-2"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880286"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106189"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22981"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16988-w"},{"key":"e_1_2_10_12_2","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1177\/088307389801301206","article-title":"Tuberous Sclerosis Complex Consensus Conference: Revised Clinical Diagnostic Criteria","volume":"13","author":"Roach E. 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