{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:40:29Z","timestamp":1790498429547,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2015-64152-R"],"award-info":[{"award-number":["SAF2015-64152-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["110837"],"award-info":[{"award-number":["110837"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70111850"],"award-info":[{"award-number":["70111850"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70112504"],"award-info":[{"award-number":["70112504"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biallelic <jats:italic>BRCA1<\/jats:italic> mutations are regarded either embryonically lethal or to cause Fanconi anemia (FA), a genomic instability syndrome characterized by bone marrow failure, developmental abnormalities, and cancer predisposition. We report biallelic <jats:italic>BRCA1<\/jats:italic> mutations c.181T\u00a0&gt;\u00a0G (p.Cys61Gly) and c.5096G\u00a0&gt;\u00a0A (p.Arg1699Gln) in a woman with breast cancer diagnosed at the age of 30\u00a0years. The common European founder mutation p.Cys61Gly confers high cancer risk, whereas the deleterious p.Arg1699Gln is hypomorphic and was suggested to confer intermediate cancer risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Aside from significant toxicity from chemotherapy, the patient showed mild FA\u2010like features (e.g., short stature, microcephaly, skin hyperpigmentation). Chromosome fragility, a hallmark of FA patient cells, was not present in patient\u2010derived peripheral blood lymphocytes. We demonstrated that the p.Arg1699Gln mutation impairs DNA double\u2010strand break repair, elevates RAD51 foci levels at baseline, and compromises BRCA1 protein function in protecting from replication stress. Although the p.Arg1699Gln mutation compromises BRCA1 function, the residual activity of the p.Arg1699Gln allele likely prevents from chromosome fragility and a more severe FA phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data expand the clinical spectrum associated with biallelic <jats:italic>BRCA1<\/jats:italic> mutations, ranging from embryonic lethality to a mild FA\u2010like phenotype and no chromosome fragility.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.863","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T03:53:54Z","timestamp":1564113234000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Biallelic germline <i>BRCA1<\/i> mutations in a patient with early onset breast cancer, mild Fanconi anemia\u2010like phenotype, and no chromosome fragility"],"prefix":"10.1002","volume":"7","author":[{"given":"Katharina","family":"Keupp","sequence":"first","affiliation":[{"name":"Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany University Hospital of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Hampp","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"H\u00fcbbel","sequence":"additional","affiliation":[{"name":"Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany University Hospital of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Maringa","sequence":"additional","affiliation":[{"name":"Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany University Hospital of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kostezka","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Rhiem","sequence":"additional","affiliation":[{"name":"Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany University Hospital of Cologne Cologne 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Genetics and Microbiology Universitat Aut\u00f2noma de Barcelona Barcelona Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Surrall\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Genetics and Biomedical Research Institute Hospital de Sant Pau Barcelona Spain"},{"name":"Department of Genetics and Microbiology Universitat Aut\u00f2noma de Barcelona Barcelona Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita K.","family":"Schmutzler","sequence":"additional","affiliation":[{"name":"Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany University Hospital of Cologne Cologne 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