ArticleAmerican journal of human genetics2018
De Novo Mutations Activating Germline TP53 in an Inherited Bone-Marrow-Failure Syndrome.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 48 citations in OpenAlex.
- Functional impact of a deep intronic variant in the RPS19 gene detected in a case of Diamond-Blackfan anemia syndrome.Haematologica · 2026Article
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- DNA Methylation Episignature as a Novel Diagnostic Tool for Diamond-Blackfan Anemia Syndrome.American journal of hematology · 2026Article
- The TP53 tumor suppressor gene: From molecular biology to clinical investigations.Journal of internal medicine · 2025Review
- Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.Annual review of pathology · 2025Review
- Germline variant affecting p53β isoforms predisposes to familial cancer.Nature communications · 2024Article
- Diagnosis, treatment, and surveillance of Diamond-Blackfan anaemia syndrome: international consensus statement.The Lancet. Haematology · 2024Article
- Regulation of p53 by the mitotic surveillance/stopwatch pathway: implications in neurodevelopment and cancer.Frontiers in cell and developmental biology · 2024Review
- The Diverse Genomic Landscape of Diamond-Blackfan Anemia: Two Novel Variants and a Mini-Review.Children (Basel, Switzerland) · 2023Review
- p53 in the Molecular Circuitry of Bone Marrow Failure Syndromes.International journal of molecular sciences · 2023Review
- A systematic approach identifies p53-DREAM pathway target genes associated with blood or brain abnormalities.Disease models & mechanisms · 2023Article
- An RPS19-edited model for Diamond-Blackfan anemia reveals TP53-dependent impairment of hematopoietic stem cell activity.JCI insight · 2023Article
- Emerging bone marrow failure syndromes- new pieces to an unsolved puzzle.Frontiers in oncology · 2023Review
- Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity.Developmental cell · 2021Article
- Non-Structural Protein 5 of Zika Virus Interacts with p53 in Human Neural Progenitor Cells and Induces p53-Mediated Apoptosis.Virologica Sinica · 2021Article
- Increased p53 signaling impairs neural differentiation in HUWE1-promoted intellectual disabilities.Cell reports. Medicine · 2021Article
- Article
- Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia.Science translational medicine · 2020Article
- Diamond-Blackfan anemia.Blood · 2020Review
- Germline mutation ofScience advances · 2020Article
Corrections and comments
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Authors and funding
39 authors at 13 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inherited bone-marrow-failure syndromes (IBMFSs) include heterogeneous genetic disorders characterized by bone-marrow failure, congenital anomalies, and an increased risk of malignancy. Many lines of evidence have suggested that p53 activation might be central to the pathogenesis of IBMFSs, including Diamond-Blackfan anemia (DBA) and dyskeratosis congenita (DC). However, the exact role of p53 activation in each clinical feature remains unknown. Here, we report unique de novo TP53 germline variants found in two individuals with an IBMFS accompanied by hypogammaglobulinemia, growth retardation, and microcephaly mimicking DBA and DC. TP53 is a tumor-suppressor gene most frequently mutated in human cancers, and occasional germline variants occur in Li-Fraumeni cancer-predisposition syndrome. Most of these mutations affect the core DNA-binding domain, leading to compromised transcriptional activities. In contrast, the variants found in the two individuals studied here caused the same truncation of the protein, resulting in the loss of 32 residues from the C-terminal domain (CTD). Unexpectedly, the p53 mutant had augmented transcriptional activities, an observation not previously described in humans. When we expressed this mutant in zebrafish and human-induced pluripotent stem cells, we observed impaired erythrocyte production. These findings together with close similarities to published knock-in mouse models of TP53 lacking the CTD demonstrate that the CTD-truncation mutations of TP53 cause IBMFS, providing important insights into the previously postulated connection between p53 and IBMFSs.
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