{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:30:16Z","timestamp":1793374216894,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":181,"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":["International Journal of Genomics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cardiac rhabdomyomas (CRs) are one of the typical phenotypes of tuberous sclerosis complex (TSC) diseases. Patients with CR could present various phenotypes and different severities.\n                      <jats:italic>TSC1<\/jats:italic>\n                      and\n                      <jats:italic>TSC2<\/jats:italic>\n                      are candidate genes for TSC. The genotype and phenotype relationship of the CR phenotype in TSC is unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TSC1<\/jats:italic>\n                      and\n                      <jats:italic>TSC2<\/jats:italic>\n                      pathogenic and likely pathogenic variants from the HGMD, ClinVar, and LOVD databases were identified (last date: 2024.12.01). After critical exclusion criteria and pathogenicity reanalyses, statistical analyses were performed for enrichment evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this study, 1250 variants of\n                      <jats:italic>TSC1<\/jats:italic>\n                      were finally included, and 26 variants (20.8%) were reported to cause the CR phenotype. In Exon 15, 5.1% of them were CR\u2010related (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), and 7.1% of them were enriched in Exon 18 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.008). After adjusting by the Benjamini\u2013Hochberg FDR method, the FDR\u2010adjusted\n                      <jats:italic>p<\/jats:italic>\n                      values were still significant for Exon 15 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.006) and Exon 18 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.028). Considering the size of each exon, there is no significant enrichment by Poisson model analysis. We included 2690 variants of\n                      <jats:italic>TSC2<\/jats:italic>\n                      ; 117 variants (4.3%) were reported to cause the CR phenotype. In Exon 41, 12% of variants were CR\u2010related (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003). The FDR\u2010adjusted\n                      <jats:italic>p<\/jats:italic>\n                      value was not significant for Exon 41 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.11). Considering the size of each exon, in Poisson model analysis, there are significant enrichments detected in Exon 37 (IRR = 2.72 [1.42, 5.19],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003), Exon 38 (IRR = 3.26 [1.65, 6.44],\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001), and Exon 41 (IRR = 5.79 [3.11, 10.77],\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). After adjusting by the Benjamini\u2013Hochberg FDR method, significant differences remained in these three exons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CR phenotypes demonstrated partial enrichment in specific exons, highlighting the importance of exon\u2010level interpretation during genetic counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijog\/2204583","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:58:53Z","timestamp":1782975533000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genotype and Cardiac Rhabdomyoma Phenotype Analyses in Tuberous Sclerosis Complex 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