A Novel Variant in the TP53 Gene Causing Li–Fraumeni Syndrome
Bibliographic Data
| ID | 15717876 |
|---|---|
| Authors | Dimitrios T Papadimitriou (0000-0002-6083-3560, Aretaeio Hospital, corresponding author), Constantine A Stratakis (0000-0002-4058-5520, National Institutes of Health), Antonis Kattamis (0000-0002-5178-0655, National and Kapodistrian University of Athens), Stavros Glentis (0000-0002-9217-052X, National and Kapodistrian University of Athens), Constantine Dimitrakakis (0000-0002-4615-1969, National and Kapodistrian University of Athens), George Spyridis (Mitera Hospital), Panagiotis Christopoulos (0000-0003-4112-8396, Aretaeio Hospital), George Mastorakos (0000-0002-1929-3275, Aretaeio Hospital), Nikolaos Vlahos (0000-0001-8479-6517, Aretaeio Hospital), Nicoletta Iacovidou (0000-0001-8021-6191, National and Kapodistrian University of Athens, corresponding author) |
| Year | 2023 |
| Volume | 10 |
| Issue | 7 |
| Pages | 1150-1150 |
| Publication date | 2023-06-30 |
| Open Access | Yes |
| Type | ARTICLE |
| Venue | Children (JOURNAL) |
| Journal identifiers | ISSN: 2227-9067 • E-ISSN: 2227-9067 |
| Publisher | Multidisciplinary Digital Publishing Institute (PUBLISHER • CH) |
| DOI | 10.3390/children10071150 |
| PMID | 37508646 |
| OpenAlex | W4382652500 |
| Language | EN |
| References cited | 2 |
Li-Fraumeni 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
Adrenocortical carcinoma · Biology · Breast cancer · Cancer · Endometrial cancer · Family history · Frameshift mutation · Gene · Germline · Germline mutation · Li–Fraumeni syndrome · Mutation · Cancer-related Molecular Pathways · Hedgehog Signaling Pathway Studies · Medicine · Virus-based gene therapy research · Genetics · Internal Medicine
| Highly cited | No |
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