{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:25:04Z","timestamp":1790835904191,"version":"4.1.0"},"reference-count":31,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder present in 1 in 8000 people and associated with arteriovenous malformations. Genetic testing can identify individuals at risk of developing the disease and is a useful diagnostic tool.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Objective:<\/jats:bold> To present a strategy for mutation detection in families clinically diagnosed with HHT.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> An optimised strategy for detecting mutations that predispose to HHT is presented. The strategy includes quantitative multiplex polymerase chain reaction, sequence analysis, RNA analysis, validation of missense mutations by amino acid conservation analysis for the <jats:italic>ENG<\/jats:italic> (<jats:italic>endoglin<\/jats:italic>) and <jats:italic>ACVRL1<\/jats:italic> (<jats:italic>ALK1<\/jats:italic>) genes, and analysis of an <jats:italic>ACVRL1<\/jats:italic> protein structural model. If no causative <jats:italic>ENG<\/jats:italic> or <jats:italic>ACVRL1<\/jats:italic> mutation is found, proband samples are referred for sequence analysis of <jats:italic>MADH4<\/jats:italic> (associated with a combined syndrome of juvenile polyposis and HHT).<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> Data obtained over the past eight years were summarised and 16 novel mutations described. Mutations were identified in 155 of 194 families with a confirmed clinical diagnosis (80% sensitivity). Of 155 mutations identified, 94 were in <jats:italic>ENG<\/jats:italic> (61%), 58 in <jats:italic>ACVRL1<\/jats:italic> (37%), and three in <jats:italic>MADH4<\/jats:italic> (2%).<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusions:<\/jats:bold> For most missense variants of <jats:italic>ENG<\/jats:italic> and <jats:italic>ACVRL1<\/jats:italic> reported to date, study of amino acid conservation showed good concordance between prediction of altered protein function and disease occurrence. The 39 families (20%) yet to be resolved may carry <jats:italic>ENG<\/jats:italic>, <jats:italic>ACVRL1<\/jats:italic>, or <jats:italic>MADH4<\/jats:italic> mutations too complex or difficult to detect, or mutations in genes yet to be identified.<\/jats:p>","DOI":"10.1136\/jmg.2006.042606","type":"journal-article","created":{"date-parts":[[2006,5,12]],"date-time":"2006-05-12T03:51:29Z","timestamp":1147405889000},"page":"722-728","source":"Crossref","is-referenced-by-count":109,"title":["Hereditary haemorrhagic telangiectasia: mutation detection, test sensitivity and novel mutations"],"prefix":"10.1136","volume":"43","author":[{"given":"N L","family":"Prigoda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Savas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S 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