133172 20260217205508.0 doi 10.3389/fgene.2023.1274108 sideral 137889 ART-2024-137889 eng Alonso, Natalia Association between missense variants of uncertain significance in the CHEK2 gene and hereditary breast cancer: a cosegregation and bioinformatics analysis 2024 Access copy available to the general public Unrestricted Inherited mutations in the CHEK2 gene have been associated with an increased lifetime risk of developing breast cancer (BC). We aim to identify in the study population the prevalence of mutations in the CHEK2 gene in diagnosed BC patients, evaluate the phenotypic characteristics of the tumor and family history, and predict the deleteriousness of the variants of uncertain significance (VUS). A genetic study was performed, from May 2016 to April 2020, in 396 patients diagnosed with BC at the University Hospital Lozano Blesa of Zaragoza, Spain. Patients with a genetic variant in the CHEK2 gene were selected for the study. We performed a descriptive analysis of the clinical variables, a bibliographic review of the variants, and a cosegregation study when possible. Moreover, an in-depth bioinformatics analysis of CHEK2 VUS was carried out. We identified nine genetic variants in the CHEK2 gene in 10 patients (two pathogenic variants and seven VUS). This supposes a prevalence of 0.75% and 1.77%, respectively. In all cases, there was a family history of BC in first- and/or second-degree relatives. We carried out a cosegregation study in two families, being positive in one of them. The bioinformatics analyses predicted the pathogenicity of six of the VUS. In conclusion, CHEK2 mutations have been associated with an increased risk for BC. This risk is well-established for foundation variants. However, the risk assessment for other variants is unclear. The incorporation of bioinformatics analysis provided supporting evidence of the pathogenicity of VUS. info:eu-repo/grantAgreement/ES/DGA/E45-23R info:eu-repo/grantAgreement/ES/MICINN/PID2019-107293GB-I00 info:eu-repo/grantAgreement/ES/MICINN/PID2022-141068NB-I00 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 2.8 2024 GENETICS & HEREDITY 79 / 192 = 0.411 2024 Q2 T2 0.863 2024 Genetics 2024 Q2 Molecular Medicine 2024 Q2 Genetics (clinical) 2024 Q2 6.2 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Menao, Sebastián Universidad de Zaragoza (orcid)0000-0002-1817-4549 Lastra, Rodrigo Arruebo, María (orcid)0000-0002-9336-1563 Bueso, María P. Pérez, Esther Murillo, M. Laura Álvarez, María Alonso, Alba Rebollar, Soraya Cruellas, Mara Arribas, Dolores Universidad de Zaragoza (orcid)0000-0002-3592-820X Ramos, Mónica Universidad de Zaragoza Isla, Dolores Galano-Frutos, Juan José Universidad de Zaragoza (orcid)0000-0002-1896-7805 García-Cebollada, Helena Universidad de Zaragoza (orcid)0000-0002-9590-7371 Sancho, Javier Universidad de Zaragoza (orcid)0000-0002-2879-9200 Andrés, Raquel Universidad de Zaragoza (orcid)0000-0003-0123-4274 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 1013 090 Universidad de Zaragoza Dpto. Cirugía Área Cirugía 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1002 807 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Toxicología 14 (2024), 1274108 [16 pp.] Front. genet. Frontiers in Genetics 1664-8021 1975510 http://zaguan.unizar.es/record/133172/files/texto_completo.pdf Versión publicada 2302345 http://zaguan.unizar.es/record/133172/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:133172 articulos driver 2026-02-17-20:24:19 ARTICLE