Background: Genome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the gene. Despite its well-established role in homologous recombination, germline mutations in are rarely reported.
Case Presentation: In this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in , , and . Importantly, her paired peripheral blood cells harbored a germline mutation, , which was also found in her father. Unfortunately, the status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation.
Conclusion: This case highlights a rare germline mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types.
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http://dx.doi.org/10.3389/fonc.2024.1380093 | DOI Listing |
Genes (Basel)
January 2025
Department of Chemistry, The RNA Institute, University at Albany, SUNY, 1400 Washington Ave Extension, Albany, NY 12222, USA.
The notion of RNA-based therapeutics has gained wide attractions in both academic and commercial institutions. RNA is a polymer of nucleic acids that has been proven to be impressively versatile, dating to its hypothesized RNA World origins, evidenced by its enzymatic roles in facilitating DNA replication, mRNA decay, and protein synthesis. This is underscored through the activities of riboswitches, spliceosomes, ribosomes, and telomerases.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, 117198 Moscow, Russia.
The advent of next-generation sequencing (NGS) has revolutionized the analysis of genetic data, enabling rapid identification of pathogenic variants in patients with inborn errors of immunity (IEI). Sometimes, the use of NGS-based technologies is associated with challenges in the evaluation of the clinical significance of novel genetic variants. In silico prediction tools, such as SpliceAI neural network, are often used as a first-tier approach for the primary examination of genetic variants of uncertain clinical significance.
View Article and Find Full Text PDFJ Clin Immunol
January 2025
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children´s Medical Center, Tehran University of Medical Sciences, 62 Qarib St., Keshavarz Blvd, Tehran, 14194, Iran.
Background: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.
View Article and Find Full Text PDFBiomedica
December 2024
Universidad del Valle, Cali, ColombiaDepartamento de Microbiología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disorders, National Institutes of Health, Bethesda, MD, USA.
Activated phosphoinositide 3-kinase δ syndrome is an inborn error of immunity due to mutations within the genes responsible for encoding PI3Kδ subunits. This syndrome results in an excessive activation of the phosphoinositide 3-kinase signaling pathway. Gainof-function mutations in the gene PIK3R1 (encoding p85α, p55α, and p50α) lead to the development of the activated PI3K δ syndrome.
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