{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:55:17Z","timestamp":1788386117461,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,3,23]],"date-time":"2006-03-23T00:00:00Z","timestamp":1143072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2006,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To determine the frequency, mutation spectrum and phenotype of the recently described autosomal recessive <jats:italic>MUTYH<\/jats:italic>\u2010associated polyposis (MAP), we performed a systematic search for <jats:italic>MUTYH (MYH<\/jats:italic>) mutations by sequencing the complete coding region of the gene in 329 unselected <jats:italic>APC<\/jats:italic> mutation\u2010negative index patients with the clinical diagnosis of familial adenomatous polyposis (FAP) or attenuated FAP (AFAP). Biallelic germline mutations in <jats:italic>MUTYH<\/jats:italic> were identified in 55 of the 329 unselected patients (17%) and in another 9 selected index cases. About one\u2010fifth (20%) of the 64 unrelated MAP patients harboured none of the 2 hot\u2010spot missense mutations Y165C and\/or G382D. Including 7 affected relatives, almost all MAP patients presented with either an attenuated (80%) or with an atypical phenotype (18%). Fifty percentage of the MAP patients had colorectal cancer at diagnosis. Duodenal polyposis was found in 18%, thyroid and stomach cancer in 1 case, other extraintestinal manifestations associated with FAP were not observed. In 8 families, vertical segregation was suspected; in 2 of these families, biallelic mutations were identified in 2 generations. Monoallelic changes with predicted functional relevance were found in 0.9% of the 329 patients, which is in accordance with the carrier frequency in the general population. In conclusion, biallelic <jats:italic>MUTYH<\/jats:italic> mutations are the underlying genetic basis in a substantial fraction of patients with adenomatous polyposis. The phenotype of MAP is best characterised as attenuated or atypical, respectively. Colorectal surveillance starting at about 18 years of age is recommended for biallelic mutation carriers and siblings of MAP patients, who refuse predictive testing. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.21905","type":"journal-article","created":{"date-parts":[[2006,3,24]],"date-time":"2006-03-24T01:18:47Z","timestamp":1143163127000},"page":"807-814","source":"Crossref","is-referenced-by-count":166,"title":["<i>MUTYH<\/i>\u2010associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical 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