{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T11:55:04Z","timestamp":1774439704958,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"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":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the formation of hamartomas in the brain, kidney, and heart, along with other complex clinical manifestations, including TSC\u2010associated neuropsychiatric disorder (TAND). Development of genotype\u2013phenotype correlations within TSC can aid clinicians in providing prognostic data and improve clinical management. We present here a multigenerational family who has a pathogenic variant in\n                      <jats:italic>TSC2<\/jats:italic>\n                      displaying a severe renal phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A 23\u2010year\u2010old Caucasian male (Patient 1) was determined to have a molecularly confirmed diagnosis of TSC at approximately 2\u2009months of age. The nonsense pathogenic variant (c.1372C&gt;T (p.Arg458*)) in\n                      <jats:italic>TSC2<\/jats:italic>\n                      had been previously identified in his father (Patient 6), grandmother (Patient 5), and other extended paternal family members (Patient 2, 3, 4, 7).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clinical evaluations revealed that the affected family members display a severe renal phenotype characterized by large angiomyolipoma burden (AMLs), renal cystic disease, and chronic kidney disease leading to renal failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our clinical report is of significance as it illustrates a possible genotype\u2013phenotype correlation between a specific\n                      <jats:italic>TSC2<\/jats:italic>\n                      pathogenic variant and a severe renal phenotype. Our case series highlights the importance of establishing genotype\u2013phenotype interactions to provide anticipatory guidance using prognostic data and clinical management.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70205","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T05:25:58Z","timestamp":1771651558000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe Renal Phenotype Across A Multigenerational Tuberous Sclerosis Complex (\n                    <scp>TSC<\/scp>\n                    ) Family"],"prefix":"10.1002","volume":"14","author":[{"given":"Elena","family":"Tuller","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics McGovern Medical School at UTHealth Houston, and Children's Memorial Hermann Hospital  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5682-4701","authenticated-orcid":false,"given":"Joshua A.","family":"Samuels","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology and Hypertension, Department of Pediatrics McGovern Medical School at UTHealth Houston, and Children's Memorial Hermann Hospital  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hope","family":"Northrup","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics McGovern Medical School at UTHealth Houston, and Children's Memorial Hermann Hospital  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0842-357X","authenticated-orcid":false,"given":"Kate","family":"Richardson","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics McGovern Medical School at UTHealth Houston, and Children's Memorial Hermann Hospital  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738040190091101"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31803068c7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(12)61767\u2010X"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2015.10.002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38083"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2023.147566"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38027"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2019.37.7_suppl.560"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2011.02.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21037"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.5.347"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12680"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010022\u201002266\u20100"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.010835"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010024\u201000818\u20100"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2021.07.011"},{"key":"e_1_2_9_18_1","volume-title":"GeneReviews","author":"Northrup H.","year":"2024"},{"key":"e_1_2_9_19_1","volume-title":"Everolimus [Package Insert]","author":"Novartis","year":"2021"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0b013e3182104347"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000073272.47681.BB"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31651"},{"issue":"21","key":"e_1_2_9_23_1","first-page":"4766","article-title":"Hamartin, the Product of the Tuberous Sclerosis 1 (TSC1) Gene, Interacts with Tuberin and Appears to Be Localized to Cytoplasmic Vesicles","volume":"58","author":"Plank T. L.","year":"1998","journal-title":"Cancer Research"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5327.805"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399\u20100004.2011.01648.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/pas.0000000000000237"},{"key":"e_1_2_9_27_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\/mgg3.70205","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.70205","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T08:35:32Z","timestamp":1774427732000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/mgg3.70205"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70205","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"assertion":[{"value":"2025-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70205"}}