{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:15:26Z","timestamp":1760728526517,"version":"build-2065373602"},"reference-count":29,"publisher":"BMJ","issue":"5","funder":[{"name":"Copenhagen University Hospital, Rigshospitalet, Denmark"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2022,8,22]]},"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background and aims<\/jats:title>\n                  <jats:p>Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition characterised by recurrent epistaxis, telangiectatic lesions in the skin and mucosal membranes, and arteriovenous malformations (AVMs) in various organs. In 3%\u20135% of patients, HHT is caused by pathogenic germline variants (PVs) in <jats:italic>SMAD4<\/jats:italic>, and these patients often have additional symptoms of juvenile polyposis syndrome and thoracic aneurysms. The phenotypic spectrum of <jats:italic>SMAD4<\/jats:italic>-associated HHT is less known, including the penetrance and severity of HHT. We aimed to investigate the phenotypic spectrum of HHT manifestations in Danish patients with PVs in <jats:italic>SMAD4<\/jats:italic> and compare the findings with current literature.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The study is a retrospective nationwide study with all known Danish patients with PVs in <jats:italic>SMAD4<\/jats:italic>. In total, 35 patients were included. The patients were identified by collecting data from genetic laboratories, various databases and clinical genetic departments across the country. Clinical information was mainly collected from the Danish HHT-Centre at Odense University Hospital.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty-nine patients with PVs in <jats:italic>SMAD4<\/jats:italic> (83%) were seen at the HHT-Centre. Seventy-six per cent of these fulfilled the Cura\u00e7ao criteria, 86% experienced recurrent epistaxis and 83% presented with telangiectatic lesions at different anatomical localisations. Almost 60% had AVMs, mainly pulmonary and hepatic, while none was found to have cerebral AVMs. Fifteen per cent had thoracic aortic abnormalities.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We present a nationwide study of one of the largest populations of patients with PVs in <jats:italic>SMAD4<\/jats:italic> that has systematically been examined for HHT manifestations. The patients presented the full spectrum of HHT-related manifestations and the majority fulfilled the Cura\u00e7ao criteria.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2022-108766","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T13:26:38Z","timestamp":1661779598000},"page":"464-468","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Hereditary haemorrhagic telangiectasia in Danish patients with pathogenic variants in <i>SMAD4:<\/i> a nationwide study"],"prefix":"10.1136","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0916-4517","authenticated-orcid":false,"given":"Anne Marie","family":"Jelsig","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anette","family":"Kjeldsen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology HHT-Centre, Odense University Hospital, Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lise Lotte","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Aarhus Universitetshospital, Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitte","family":"Bertelsen","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G\u00e1sdal","family":"Karstensen","sequence":"additional","affiliation":[{"name":"Danish Polyposis Registry, Gastro Unit, Hvidovre Hospital, Hvidovre, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Brusgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense Universitetshospital, Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pernille M","family":"Torring","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense Universitetshospital, Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,8,29]]},"reference":[{"key":"2025101711404435000_60.5.464.1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000306)91:1<66::AID-AJMG12>3.0.CO;2-P"},{"key":"2025101711404435000_60.5.464.2","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1038\/s41436-020-0775-8","article-title":"Cura\u00e7ao diagnostic criteria for hereditary hemorrhagic telangiectasia is highly predictive of a pathogenic variant in 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