{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:00:16Z","timestamp":1779908416454,"version":"3.53.1"},"reference-count":17,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Background and Clinical Significance: Inherited thrombocytopenia (IT) is a heterogeneous group of disorders caused by mutations in over 45 genes. Among these, ANKRD26-related thrombocytopenia (ANKRD26-RT) accounts for a notable subset and is associated with variable bleeding tendencies and an increased risk of myeloid malignancies. However, the extent of this oncogenic risk appears to vary between specific gene variants. Understanding the genotype\u2013phenotype relationship is essential for patient counseling and management. This report presents a multigenerational family carrying the rare c.\u2212118C &gt; G variant in the 5\u2032 untranslated region of ANKRD26, contributing to the discussion on variant-specific cancer predisposition. Case Presentation: Two sisters aged 57 and 60 presented with lifelong bleeding diathesis and moderate thrombocytopenia. Their symptoms included easy bruising, menorrhagia, and excessive postoperative bleeding. Genetic testing confirmed heterozygosity for the ANKRD26 c.\u2212118C &gt; G variant. Bone marrow analysis revealed abnormal megakaryopoiesis without evidence of dysplasia or somatic mutations. One sister underwent major surgery without complications when managed with prophylactic hemostatic therapy. Their family history included multiple female relatives with similar symptoms, although formal testing was limited. Notably, none of the affected individuals developed hematologic malignancy, and only one developed esophageal cancer, with no current evidence linking this variant to solid tumors. Conclusions: This case underscores the importance of distinguishing between ANKRD26 variants when assessing malignancy risk. While ANKRD26-RT is associated with myeloid neoplasms, the c.\u2212118C &gt; G variant may confer a lower oncogenic potential. Variant-specific risk stratification and genetic counseling are crucial for optimizing surveillance and avoiding unnecessary interventions in low-risk individuals.<\/jats:p>","DOI":"10.3390\/hematolrep17040037","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T11:58:53Z","timestamp":1753358333000},"page":"37","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["ANKRD26 Gene Mutation and Thrombocytopenia\u2014Is the Risk of Malignancy Dependent on the Mutation Variant?"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3333-8449","authenticated-orcid":false,"given":"Eirik B.","family":"Tj\u00f8nnfjord","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, \u00d8stfold Hospital Trust, 1714 Gr\u00e5lum, Norway"},{"name":"Department of Haematology, Oslo University Hospital, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1316-5843","authenticated-orcid":false,"given":"Kristian","family":"Tveten","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe","family":"Spetalen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Oslo University Hospital, 0372 Oslo, Norway"},{"name":"Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geir E.","family":"Tj\u00f8nnfjord","sequence":"additional","affiliation":[{"name":"Department of Haematology, Oslo University Hospital, 0372 Oslo, Norway"},{"name":"Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway"},{"name":"Section of Cancer Cytogenetics, Institute of Cancer Genetics and Informatics, Oslo University Hospital, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1182\/asheducation-2017.1.385","article-title":"Hereditary thrombocytopenias: A growing list of disorders","volume":"2017","author":"Noris","year":"2017","journal-title":"Hematology Am. Soc. Hematol. Educ. Program"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1182\/blood.2020009300","article-title":"Genetics of inherited thrombocytopenias","volume":"139","author":"Warren","year":"2022","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lassandro, G., Palladino, V., Faleschini, M., Barone, A., Boscarol, G., Cesaro, S., Chiocca, E., Farruggia, P., Giona, F., and Gorio, C. (2022). \u201cChildren with Inherited Platelet disorders Surveillance\u201d (CHIPS) retrospective and prospective observational cohort study by Italian Association of Pediatric Hematology and Oncology (AIEOP). Front. Genet., 10.","DOI":"10.3389\/fped.2022.967417"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s11899-022-00666-4","article-title":"ANKRD26-Related Thrombocytopenia and Predisposition to Myeloid Neoplasms","volume":"17","author":"Sullivan","year":"2022","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6673","DOI":"10.1182\/blood-2011-02-336537","article-title":"Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: Analysis of 78 patients from 21 families","volume":"117","author":"Noris","year":"2011","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ajhg.2010.12.006","article-title":"Mutations in the 5\u2032UTR of ANKRD26, the ankirin repeat domain 26 gene, cause an autosomal-dominant for of inherited thrombocytopenia, THC2","volume":"88","author":"Pippucci","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1182\/blood-2013-04-499319","article-title":"ANKRD26-realted thrombocytopenia and myeloid malignancies","volume":"122","author":"Noris","year":"2013","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1080\/09537104.2022.2071853","article-title":"Prevalence and natural history of variants in the ANKRD26 gene: A short review and update of reported cases","volume":"33","author":"Vyas","year":"2022","journal-title":"Platelets"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13045-016-0382-y","article-title":"5\u2032UTR point substitution and N-terminal truncating mutations of ANKRD26 in acute myeloid leukemia","volume":"10","author":"Marconi","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e20210444","DOI":"10.1084\/jem.20210444","article-title":"Familial thrombocytopenia due to complex structural resulting in a WAC-ANKRD26 fusion transcript","volume":"218","author":"Wahlster","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1007\/s00277-019-03632-y","article-title":"A novel nucleotide substitution in the 5\u2032 untranslated region of ANKRD26 gene is associated with inherited thrombocytopenia: A report of two new families","volume":"98","author":"Diep","year":"2019","journal-title":"Ann. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1182\/blood.2018891192","article-title":"Diagnostic high throughput sequencing of 2396 patients with bleeding, trombotic and plateles disorders","volume":"134","author":"Downes","year":"2019","journal-title":"Blood"},{"key":"ref_13","unstructured":"(2025, July 23). Expression of ANKRD26 in Cancer\u2014Summary\u2014The Human Protein Atlas. Proteinatlas.org. Available online: https:\/\/www.proteinatlas.org\/ENSG00000107890-ANKRD26\/cancer."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hofbrucker-MacKenzie, S.A., Englisch, A.S., Izadi, M., Metzner, K., Kessels, M.M., and Qualmann, B. (2022). Ankrd26 is critical for cell differentiation and cancer-linked mutations affect its key properties. bioRxiv.","DOI":"10.1101\/2021.05.19.444897"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1080\/09537104.2020.1790512","article-title":"Relation between mutations in the 5\u2032 UTR of ANKRD26 gene and inherited thrombocytopenia with predisposition to myeloid malignancies. An Egyptian study","volume":"32","author":"Zidan","year":"2021","journal-title":"Platelets"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.3109\/10428194.2014.903476","article-title":"A new family with a germline ANKRD26 mutation and predisposition to myeloid malignancies","volume":"55","author":"Marquez","year":"2014","journal-title":"Leuk. Lymphoma"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1007\/s00431-015-2549-x","article-title":"Childhood diagnosis of genetic thrombocytopenia with mutation in the ankyrine repeat domain 26 gene","volume":"174","author":"Boutroux","year":"2015","journal-title":"Eur. J. Pediatr."}],"container-title":["Hematology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2038-8330\/17\/4\/37\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:15:17Z","timestamp":1760033717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2038-8330\/17\/4\/37"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":17,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["hematolrep17040037"],"URL":"https:\/\/doi.org\/10.3390\/hematolrep17040037","relation":{},"ISSN":["2038-8330"],"issn-type":[{"value":"2038-8330","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,24]]}}}