{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:17:28Z","timestamp":1760149048423,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Li\u2013Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline pathogenic variants in the tumor protein p53 (TP53) gene and elevated risk of a broad range of early-onset malignancies. Patients with LFS are at risk of a second and third primary tumor. A 15-month-old girl consulted for clitoromegaly and pubic hair. Adrenal ultrasound detected a large left adrenal tumor. Left total adrenalectomy confirmed adrenocortical carcinoma. Family history revealed multiple highly malignant neoplasms at an early age across five generations, and a genetic dominant trait seemed probable. Whole-genome sequencing was performed. Multiple members of the family were found positive for a novel likely pathogenic variant (c. 892delGinsTTT, p. Glu298PhefsX48, NM_000546.6) in the TP53 gene, causing the loss of normal protein function through non-sense-mediated mRNA decay. According to the PSV1 supporting criteria and the Auto PVS1 online tool this frameshift variant: hg19\/17-7577045-TC-TAAA:NM_000546.6 has a very strong, definitive clinical validity for LFS with autosomal dominant inheritance. Proper guidance resulted in timely diagnosis of a second tumor (primary osteosarcoma) in the index case and in the early detection of breast and cervical cancer in her young mother. Patients with cancer predisposition syndromes like LFS require close multidisciplinary cancer surveillance and appropriate referral to expert centers.<\/jats:p>","DOI":"10.3390\/children10071150","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T16:06:37Z","timestamp":1688141197000},"page":"1150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel Variant in the TP53 Gene Causing Li\u2013Fraumeni Syndrome"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6083-3560","authenticated-orcid":false,"given":"Dimitrios T.","family":"Papadimitriou","sequence":"first","affiliation":[{"name":"Endocrine Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, 11528 Athens, Greece"},{"name":"Pediatric\u2013Adolescent Endocrinology and Diabetes, Athens Medical Center, 15125 Marousi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4058-5520","authenticated-orcid":false,"given":"Constantine A.","family":"Stratakis","sequence":"additional","affiliation":[{"name":"Section on Endocrinology & Genetics, The Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD 20814, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5178-0655","authenticated-orcid":false,"given":"Antonis","family":"Kattamis","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, First Department of Pediatrics, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"\u2018Aghia Sophia\u2019 Children\u2019s Hospital ERN-Genturis Center, 11527 Athina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9217-052X","authenticated-orcid":false,"given":"Stavros","family":"Glentis","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, First Department of Pediatrics, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"\u2018Aghia Sophia\u2019 Children\u2019s Hospital ERN-Genturis Center, 11527 Athina, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4615-1969","authenticated-orcid":false,"given":"Constantine","family":"Dimitrakakis","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Alexandra University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George P.","family":"Spyridis","sequence":"additional","affiliation":[{"name":"Surgical Pediatric Oncology, Mitera Children\u2019s Hospital, 15123 Marousi, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4112-8396","authenticated-orcid":false,"given":"Panagiotis","family":"Christopoulos","sequence":"additional","affiliation":[{"name":"Pediatric Gynecology Unit, Aretaieion Hospital, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1929-3275","authenticated-orcid":false,"given":"George","family":"Mastorakos","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8479-6517","authenticated-orcid":false,"given":"Nikolaos F.","family":"Vlahos","sequence":"additional","affiliation":[{"name":"Second Department of Obstetrics and Gynecology, Aretaieion Hospital, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8021-6191","authenticated-orcid":false,"given":"Nicoletta","family":"Iacovidou","sequence":"additional","affiliation":[{"name":"Neonatal Department, Aretaieion Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5975","DOI":"10.1038\/s41388-021-01991-3","article-title":"Spontaneous and inherited TP53 genetic alterations","volume":"40","author":"Levine","year":"2021","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1158\/0008-5472.CAN-19-0728","article-title":"Penetrance of Different Cancer Types in Families with Li-Fraumeni Syndrome: A Validation Study Using Multicenter Cohorts","volume":"80","author":"Shin","year":"2020","journal-title":"Cancer Res."},{"key":"ref_3","unstructured":"Aedma, S.K., and Kasi, A. 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