{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:50:11Z","timestamp":1789192211481,"version":"build-2803163510"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"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"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Biallelic\n                    <jats:italic>MSH3<\/jats:italic>\n                    germline variants are a rare cause of adenomatous polyposis as yet reported in two small families only. We describe the phenotype of a third family, the largest thus far, with adenomatous polyposis related to compound heterozygous\n                    <jats:italic>MSH3<\/jats:italic>\n                    pathogenic variants. The index patient was a 55-years old male diagnosed with rectal cancer and adenomatous polyposis (cumulatively 52 polyps), with a family history of colorectal polyposis with unknown cause. Next-generation sequencing and copy number variation analysis of a panel of genes associated with colorectal cancer and polyposis revealed compound heterozygous germline pathogenic variants in the\n                    <jats:italic>MSH3<\/jats:italic>\n                    gene. Nine out of 11 siblings were genotyped. Three siblings carried the same compound heterozygous\n                    <jats:italic>MSH3<\/jats:italic>\n                    variants. Colonoscopy screening showed predominantly right-sided adenomatous polyposis in all compound heterozygous siblings, with a cumulative number of adenomas ranging from 18 to 54 in an average of four colonoscopies, and age at first adenoma detection ranging from 46 to 59. Microsatellite analysis demonstrated alterations at selected tetranucleotide repeats (EMAST) in DNA retrieved from the rectal adenocarcinoma, colorectal adenomas as well as of normal colonic mucosa. Gastro-duodenoscopy did not reveal adenomas in any of the four patients. Extra-intestinal findings included a ductal adenocarcinoma in ectopic breast tissue in one female sibling at the age of 46, and liver cysts in three affected siblings. None of the three heterozygous or wild type siblings who previously underwent colonoscopy had adenomatous polyposis. We conclude that biallelic variants in\n                    <jats:italic>MSH3<\/jats:italic>\n                    are a rare cause of attenuated adenomatous polyposis with an onset in middle age.\n                  <\/jats:p>","DOI":"10.1007\/s10689-022-00297-x","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T03:14:31Z","timestamp":1654658071000},"page":"49-54","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A large family with MSH3-related polyposis"],"prefix":"10.1007","volume":"22","author":[{"given":"Arthur S.","family":"Aelvoet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00ebl R.","family":"Hoekman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert J. W.","family":"Redeker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitske","family":"Weegenaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"Dekker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carel J. M.","family":"van Noesel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floor A. M.","family":"Duijkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"issue":"5","key":"297_CR1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1007\/s004399900153","volume":"105","author":"L Spirio","year":"1999","unstructured":"Spirio L, Green J, Robertson J, Robertson M, Otterud B, Sheldon J et al (1999) The identical 5\u2019 splice-site acceptor mutation in five attenuated APC families from Newfoundland demonstrates a founder effect. Hum Genet 105(5):388\u2013398","journal-title":"Hum Genet"},{"issue":"9377","key":"297_CR2","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S0140-6736(03)13805-6","volume":"362","author":"JR Sampson","year":"2003","unstructured":"Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG et al (2003) Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. 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Genet Med 17(5):405\u2013424","journal-title":"Genet Med"},{"issue":"2","key":"297_CR9","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s00439-008-0542-4","volume":"124","author":"K Wimmer","year":"2008","unstructured":"Wimmer K, Etzler J (2008) Constitutional mismatch repair-deficiency syndrome: have we so far seen only the tip of an iceberg? Hum Genet 124(2):105\u2013122","journal-title":"Hum Genet"},{"key":"297_CR10","doi-asserted-by":"crossref","unstructured":"Perne C, Peters S, Cartolano M, Horpaopan S, Grimm C, Altm\u00fcller J et al (2021) Variant profiling of colorectal adenomas from three patients of two families with MSH3-related adenomatous polyposis. 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Aelvoet, Dani\u00ebl R. Hoekman, Bert J.W. Redeker, Jitske Weegenaar, Carel J.M. van Noesel and Floor A.M. Duijkers: None to declare. Evelien Dekker: endoscopic equipment on loan of FujiFilm and Olympus, received a research grant from FujiFilm. I have received honorarium for consultancy from FujiFilm, Olympus, GI Supply, PAION and Ambu, and speakers' fees from Olympus, GI Supply, Norgine, IPSEN, PAION and FujiFilm.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was assessed by the Institutional Review Board of Amsterdam UMC, location AMC, and was not found to be subjected to the legislation Medical Research Involving Human Subjects Act.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"A written informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The participants have consented to the submission of an article about their family to a scientific journal.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research or publication funding"}}]}}