{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:03:51Z","timestamp":1791216231987,"version":"4.1.0"},"reference-count":36,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2006,10]]},"abstract":"\n Background:<\/jats:bold>\n Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disease exhibiting multifocal vascular telangiectases and arteriovenous malformations. The majority of cases are caused by mutations in either the endoglin (\n ENG<\/jats:italic>\n ) or activin receptor-like kinase 1 (\n ALK1, ACVRL1)<\/jats:italic>\n genes; both members of the transforming growth factor (TGF)-\u03b2 pathway. Mutations in\n SMAD4<\/jats:italic>\n , another TGF-\u03b2 pathway member, are seen in patients with the combined syndrome of juvenile polyposis (JP) and HHT (JP-HHT).\n <\/jats:p>\n \n Methods:<\/jats:bold>\n We sought to determine if HHT patients without any apparent history of JP, who were undergoing routine diagnostic testing, would have mutations in\n SMAD4<\/jats:italic>\n . We tested 30 unrelated HHT patients, all of whom had been referred for DNA based testing for HHT and were found to be negative for mutations in\n ENG<\/jats:italic>\n and\n ALK1<\/jats:italic>\n .\n <\/jats:p>\n \n Results:<\/jats:bold>\n Three of these people harboured mutations in\n SMAD4<\/jats:italic>\n , a rate of 10% (3\/30). The\n SMAD4<\/jats:italic>\n mutations were similar to those found in other patients with the JP-HHT syndrome.\n <\/jats:p>\n \n Conclusions:<\/jats:bold>\n The identification of\n SMAD4<\/jats:italic>\n mutations in HHT patients without prior diagnosis of JP has significant and immediate clinical implications, as these people are likely to be at risk of having JP-HHT with the associated increased risk of gastrointestinal cancer. We propose that routine DNA based testing for HHT should include\n SMAD4<\/jats:italic>\n for samples in which mutations in neither\n ENG<\/jats:italic>\n nor\n ALK1<\/jats:italic>\n are identified. HHT patients with\n SMAD4<\/jats:italic>\n mutations should be screened for colonic and gastric polyps associated with JP.\n <\/jats:p>","DOI":"10.1136\/jmg.2006.041517","type":"journal-article","created":{"date-parts":[[2006,4,13]],"date-time":"2006-04-13T20:35:44Z","timestamp":1144960544000},"page":"793-797","source":"Crossref","is-referenced-by-count":229,"title":["SMAD4<\/i>\n mutations found in unselected HHT patients"],"prefix":"10.1136","volume":"43","author":[{"given":"C J","family":"Gallione","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Richards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T G W","family":"Letteboer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Rushlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N 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