{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T04:13:36Z","timestamp":1743135216244,"version":"3.40.3"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health and Medical Research Council of Australia"},{"DOI":"10.13039\/501100000950","name":"Cancer Council South Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BJC Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Pathogenic\/likely pathogenic (P\/LP) germline variants in <jats:italic>RUNX1<\/jats:italic> cause familial platelet disorder with associated myeloid malignancies (FPDMM), also known as <jats:italic>RUNX1-<\/jats:italic>Familial Platelet Disorder (RUNX1-FPD, or FPD), a condition characterized by qualitative and quantitative platelet defects and predisposition to hematopoietic malignancies. Here, we present follow up to a case of a woman with acute myeloid leukemia and lifelong thrombocytopenia which had previously been attributed to presumptive pathogenic (P) <jats:italic>GATA2<\/jats:italic> missense variants. However, re-evaluation with updated molecular technology sensitive for detection of copy number variants (CNVs) led to the identification of a P deletion of exons 5-6 in <jats:italic>RUNX1<\/jats:italic>, which had been undetected when examined at first presentation. This case highlights the importance of comprehensive molecular evaluation and careful variant interpretation, especially regarding CNVs.<\/jats:p>","DOI":"10.1038\/s44276-024-00117-y","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:53:52Z","timestamp":1743123232000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Germline copy number variants in RUNX1: An updated case report and a decade-old red herring"],"prefix":"10.1038","volume":"3","author":[{"given":"Natalie T.","family":"Deuitch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amra","family":"Kajdic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Bresciani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marshall S.","family":"Horwitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamish S.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"Craft","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn","family":"Chong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy A.","family":"Godley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul P.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"117_CR1","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1182\/blood.2023019746","volume":"142","author":"L Cunningham","year":"2023","unstructured":"Cunningham L, Merguerian M, Calvo KR, Davis J, Deuitch NT, Dulau-Florea A, et al. Natural history study of patients with familial platelet disorder with associated myeloid malignancy. Blood. 2023;142:2146\u201358.","journal-title":"Blood"},{"key":"117_CR2","unstructured":"Deuitch N, Broadbridge E, Cunningham L, Liu P RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReviews((R)). Seattle (WA) 1993."},{"key":"117_CR3","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.jtct.2023.10.018","volume":"30","author":"LS Williams","year":"2024","unstructured":"Williams LS, Williams KM, Gillis N, Bolton K, Damm F, Deuitch NT, et al. Donor-derived malignancy and transplantation morbidity: risks of patient and donor genetics in allogeneic hematopoietic stem cell transplantation. Transplant Cell Ther. 2024;30:255\u201367.","journal-title":"Transplant Cell Ther"},{"key":"117_CR4","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1182\/blood.2022017735","volume":"141","author":"CC Homan","year":"2023","unstructured":"Homan CC, Scott HS, Brown AL. Hereditary platelet disorders associated with germ line variants in RUNX1, ETV6, and ANKRD26. Blood. 2023;141:1533\u201343.","journal-title":"Blood"},{"key":"117_CR5","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1182\/blood-2015-09-669937","volume":"127","author":"MW Wlodarski","year":"2016","unstructured":"Wlodarski MW, Hirabayashi S, Pastor V, Stary J, Hasle H, Masetti R, et al. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. Blood. 2016;127:1387\u201397.","journal-title":"Blood"},{"key":"117_CR6","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.3390\/cancers15051590","volume":"15","author":"M Santiago","year":"2023","unstructured":"Santiago M, Liquori A, Such E, Zuniga A, Cervera J. The Clinical Spectrum, Diagnosis, and Management of GATA2 Deficiency. Cancers. 2023;15:1590.","journal-title":"Cancers"},{"key":"117_CR7","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1038\/leu.2015.40","volume":"29","author":"CN Hahn","year":"2015","unstructured":"Hahn CN, Brautigan PJ, Chong CE, Janssan A, Venugopal P, Lee Y, et al. Characterisation of a compound in-cis GATA2 germline mutation in a pedigree presenting with myelodysplastic syndrome\/acute myeloid leukemia with concurrent thrombocytopenia. Leukemia. 2015;29:1795\u20137.","journal-title":"Leukemia"},{"key":"117_CR8","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/1756-8722-7-36","volume":"7","author":"J Gao","year":"2014","unstructured":"Gao J, Gentzler RD, Timms AE, Horwitz MS, Frankfurt O, Altman JK, et al. Heritable GATA2 mutations associated with familial AML-MDS: a case report and review of literature. J Hematol Oncol. 2014;7:36.","journal-title":"J Hematol Oncol"},{"key":"117_CR9","doi-asserted-by":"publisher","first-page":"2962","DOI":"10.1182\/bloodadvances.2019000644","volume":"3","author":"X Luo","year":"2019","unstructured":"Luo X, Feurstein S, Mohan S, Porter CC, Jackson SA, Keel S, et al. ClinGen Myeloid Malignancy Variant Curation Expert Panel recommendations for germline RUNX1 variants. Blood Adv. 2019;3:2962\u201379.","journal-title":"Blood Adv"},{"key":"117_CR10","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1182\/bloodadvances.2023011165","volume":"8","author":"K Yu","year":"2024","unstructured":"Yu K, Deuitch N, Merguerian M, Cunningham L, Davis J, Bresciani E, et al. Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy. Blood Adv. 2024;8:497\u2013511.","journal-title":"Blood Adv"}],"container-title":["BJC Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s44276-024-00117-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44276-024-00117-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44276-024-00117-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:53:57Z","timestamp":1743123237000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s44276-024-00117-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,27]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["117"],"URL":"https:\/\/doi.org\/10.1038\/s44276-024-00117-y","relation":{},"ISSN":["2731-9377"],"issn-type":[{"value":"2731-9377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,27]]},"assertion":[{"value":"24 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"These families are part of the NIH RUNX1 Natural History Study (19-HG0059), which has been approved by the NIH Institutional Review Board (NCT03854318). Informed consent was obtained from all enrolled participants and all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with Declaration of Helsinki, as revised in 2000.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent"}}],"article-number":"18"}}