{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:47:56Z","timestamp":1767919676587,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["n82073462"],"award-info":[{"award-number":["n82073462"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tuberous sclerosis complex (TSC), an autosomal\u2010dominant disorder, is characterized by hamartomas affecting multiple organ systems. The underlying etiology of TSC is the pathogenic variations of the <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic> genes. The phenotype variability of TSC could lead to missed diagnosis; therefore, the latest molecular diagnostic criteria for identifying a heterozygous pathogenic variant in either the <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic> gene filled this gap. Furthermore, the pathogenicity of numerous variants remains unverified, potentially leading to misinterpretations of their functional consequences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, a single patient presenting with atypical vitiligo\u2010like skin lesions suspected to have TSC was enrolled. Targeted next\u2010generation sequencing and Sanger sequencing were employed to identify a pathogenic variant. Additionally, a minigene splicing assay was conducted to assess the impact of <jats:italic>TSC1<\/jats:italic> c.1030\u20102A&gt;T, located in intron 10, on RNA splicing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel <jats:italic>TSC1<\/jats:italic>: c.1030\u20102A&gt;T heterozygosis variant was identified in intron 10. In\u00a0vitro minigene assay revealed that the c.1030\u20102A&gt;T variant caused exon 11 skipping, resulting in a frameshift in the absence of 112 base pairs of mature messenger RNA and premature termination after 174 base pairs (p.Ala344Glnfs*59).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The detection of this novel pathogenic <jats:italic>TSC1<\/jats:italic> variant in the patient with atypical vitiligo\u2010like skin lesions enrolled in our study ultimately resulted in the diagnosis of TSC. As a result, our study contributes to expanding the mutational spectrum of the <jats:italic>TSC1<\/jats:italic> gene and refining the genotype\u2013phenotype map of TSC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2403","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T06:46:51Z","timestamp":1709621211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of a novel <i>TSC1<\/i> gene variant in a patient with atypical vitiligo\u2010like skin lesions: Unveiling the hidden tuberous sclerosis complex"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7563-3895","authenticated-orcid":false,"given":"Linli","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Dermatology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Department of Dermatology Suining Central Hospital  Suining Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Langzhong People's Hospital  Nanchong Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengzhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Affiliated Hospital of North Sichuan Medical College  Nanchong Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunshui","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Suining Central Hospital  Suining Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e07903"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2014.4299"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31803068c7"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2021.104309"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.540"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1040638720905833"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2015.10.002"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.5152\/balkanmedj.2021.21092"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.13264"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1091323"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u201060761\u2010759\u20104_15"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.35"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102350\u20107\u201072"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005637"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000028666"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073807307093"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41439\u2010022\u201000181\u20101"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2021.07.011"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31651"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3928\/19382359\u201020170320\u201001"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738040190090301"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2014.938"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911175"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0929\u2010693X(22)00283\u20104"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.241"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2014.4298"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2017.11.002"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.575750"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2403","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T11:11:38Z","timestamp":1711537898000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/mgg3.2403"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2403","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2403"}}