{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T10:11:09Z","timestamp":1778235069964,"version":"3.51.4"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Familial Cancer"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Biallelic pathogenic variants in the\n                    <jats:italic>MBD4<\/jats:italic>\n                    gene have recently been associated with an autosomal recessive cancer predisposition syndrome deemed \u201c\n                    <jats:italic>MBD4<\/jats:italic>\n                    -associated neoplasia syndrome (MANS)\u201d. Early reports of individuals with MANS highlight the propensity to develop young onset colorectal polyposis and hyper-mutated acute myeloid leukemia (AML). In the following case series, we present four patients with MANS from three families with polyps and AML, as well as additional features previously less described, such as schwannoma and thyroid cancer. This series increases the total number of reported cases by 27%, with the intention of achieving a more robust understanding of the full phenotypic spectrum of MANS.\n                  <\/jats:p>","DOI":"10.1007\/s10689-026-00566-z","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T09:28:48Z","timestamp":1778232528000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biallelic germline MBD4 mutations predispose to colorectal polyposis, hypermutated AML, and schwannomas"],"prefix":"10.1007","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2532-0767","authenticated-orcid":false,"given":"Julia","family":"Cooper","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-8536","authenticated-orcid":false,"given":"Brittany L.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3791-8517","authenticated-orcid":false,"given":"Lauren","family":"Bokovitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-3614","authenticated-orcid":false,"given":"Hetty","family":"Carraway","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8325-2603","authenticated-orcid":false,"given":"Sudipto","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8632-6065","authenticated-orcid":false,"given":"David","family":"Liska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8635-3880","authenticated-orcid":false,"given":"Sumithira","family":"Vasu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5496-3839","authenticated-orcid":false,"given":"Harry","family":"Lesmana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4275-5562","authenticated-orcid":false,"given":"James S.","family":"Blachly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"566_CR1","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1182\/blood-2018-05-852566","volume":"132","author":"MA Sanders","year":"2018","unstructured":"Sanders MA et al (2018) MBD4 guards against methylation damage and germ line deficiency predisposes to clonal hematopoiesis and early-onset AML. Blood 132:1526\u20131534","journal-title":"Blood"},{"key":"566_CR2","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.ajhg.2022.03.018","volume":"109","author":"C Palles","year":"2022","unstructured":"Palles C et al (2022) Germline MBD4 deficiency causes a multi-tumor predisposition syndrome. Am J Hum Genet 109:953\u2013960","journal-title":"Am J Hum Genet"},{"key":"566_CR3","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/bjh.18178","volume":"198","author":"P Blombery","year":"2022","unstructured":"Blombery P et al (2022) Methyl-CpG binding domain 4, DNA glycosylase (MBD4)-associated neoplasia syndrome associated with a homozygous missense variant in MBD4: expansion of an emerging phenotype. Br J Haematol 198:196\u2013199","journal-title":"Br J Haematol"},{"key":"566_CR4","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1038\/s41431-023-01418-5","volume":"31","author":"M Terradas","year":"2023","unstructured":"Terradas M et al (2023) MBD4-associated neoplasia syndrome: screening of cases with suggestive phenotypes. Eur J Hum Genet 31:1185\u20131189","journal-title":"Eur J Hum Genet"},{"key":"566_CR5","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1093\/jnci\/djad248","volume":"116","author":"M-C Villy","year":"2024","unstructured":"Villy M-C et al (2024) Familial uveal melanoma and other tumors in 25 families with monoallelic germline MBD4 variants. JNCI J Natl Cancer Inst 116:580\u2013587","journal-title":"JNCI J Natl Cancer Inst"},{"key":"566_CR6","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2025.287690","author":"G Dadi","year":"2025","unstructured":"Dadi G et al (2025) A founder heterozygous mutation in Methyl-CpG binding domain protein 4 (MBD4) prevalent among Israeli Christian Arabs predisposes to increased mutagenesis. Haematologica. https:\/\/doi.org\/10.3324\/haematol.2025.287690","journal-title":"Haematologica"},{"key":"566_CR7","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/cge.70014","volume":"109","author":"I Querido","year":"2026","unstructured":"Querido I et al (2026) A novel deleterious variant and a founder effect in four new families of MBD4-Associated Neoplasia Syndrome recruited over a period of 20 years. 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