{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:11:24Z","timestamp":1783599084580,"version":"3.55.0"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,10,3]],"date-time":"2013-10-03T00:00:00Z","timestamp":1380758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:p>Hereditary haemorrhagic telangiectasia (<jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content>) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and visceral arteriovenous malformations (<jats:styled-content style=\"fixed-case\">AVM<\/jats:styled-content>). The clinical diagnosis of <jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content> is based on the Cura\u00e7ao criteria. About 85% of <jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content> patients carry mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">ENG<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">ACVRL1<\/jats:styled-content><\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">SMAD4<\/jats:styled-content><\/jats:italic> genes. Here, we report on the genetic heterogeneity in the Danish national <jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content> population and address the prevalence of pulmonary arteriovenous malformations (<jats:styled-content style=\"fixed-case\">PAVM<\/jats:styled-content>). Probands of 107 apparently unrelated families received genetic testing, including sequencing and multiplex ligation\u2010dependent probe amplification (<jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content>) analyses of <jats:italic><jats:styled-content style=\"fixed-case\">ENG<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">ACVRL1<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">SMAD4<\/jats:styled-content><\/jats:italic>. These 107 families included 320 patients confirmed to have <jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content> either clinically or genetically. In 89% of the probands (<jats:italic>n<\/jats:italic>\u2009=\u200995), a mutation was identified. We detected 64 unique mutations of which 27 (41%) were novel. Large deletions were identified in <jats:italic><jats:styled-content style=\"fixed-case\">ENG<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">ACVRL1<\/jats:styled-content><\/jats:italic>. The prevalence of <jats:styled-content style=\"fixed-case\">PAVM<\/jats:styled-content> was 52.3% in patients with an <jats:italic><jats:styled-content style=\"fixed-case\">ENG<\/jats:styled-content><\/jats:italic> mutation and 12.9% in the <jats:italic><jats:styled-content style=\"fixed-case\">ACVRL1<\/jats:styled-content><\/jats:italic> mutation carriers. We diagnosed 80% of the patients clinically, fulfilling the Cura\u00e7ao criteria, and those remaining were diagnosed by genetic testing. It is discussed when to assign pathogenicity to missense and splice site mutations. The adding of an extra criterion to the Cura\u00e7ao criteria is suggested.<\/jats:p>","DOI":"10.1111\/cge.12269","type":"journal-article","created":{"date-parts":[[2013,9,3]],"date-time":"2013-09-03T18:01:46Z","timestamp":1378231306000},"page":"123-133","source":"Crossref","is-referenced-by-count":43,"title":["National mutation study among Danish patients with hereditary haemorrhagic telangiectasia"],"prefix":"10.1111","volume":"86","author":[{"given":"P.M.","family":"T\u00f8rring","sequence":"first","affiliation":[{"name":"HHT Centre OUH, Department of Clinical Genetics"},{"name":"Department of Otorhinolaryngology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Brusgaard","sequence":"additional","affiliation":[{"name":"HHT Centre OUH, Department of Clinical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.B.","family":"Ousager","sequence":"additional","affiliation":[{"name":"HHT Centre OUH, Department of Clinical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.E.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology Odense University Hospital and Institute of Clinical Research, University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.D.","family":"Kjeldsen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.2000.00725.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.069013"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.10.5230"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.4329\/wjr.v2.i9.339"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1999.00398.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-345"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.5.1.21"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15732-2"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2004.00341.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9345"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20017"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.041517"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028712"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31450"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2005.01555.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-004-1196-5"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20342"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.042606"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-010-0825-4"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01596.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9421"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-007-0187-5"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-9-75"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2007.060117"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02531.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31101"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31802d8373"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000306)91:1<66::AID-AJMG12>3.0.CO;2-P"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35715"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.GIM.0000132689.25644.7C"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_6_34_1","unstructured":"ChaikuadA AlfanoI CooperC et al. 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