{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T12:56:13Z","timestamp":1765976173914,"version":"3.37.3"},"reference-count":13,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T00:00:00Z","timestamp":1513209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hereditary hemorrhagic telangiectasia (<jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content>) is an autosomal dominant genetic disorder caused by mutations in <jats:italic><jats:styled-content style=\"fixed-case\">ENG<\/jats:styled-content><\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">ACVRL<\/jats:styled-content>1,<\/jats:italic> or <jats:italic><jats:styled-content style=\"fixed-case\">SMAD<\/jats:styled-content>4<\/jats:italic>. Around 90% of <jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content> patients present with a heterozygous pathogenic genetic variation. Almost all cases of <jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content> have a family history. Very few cases are de novo or mosaicism. We describe a case with mutational mosaicism that would not be observed in the clinical routine when using Sanger sequencing or a <jats:styled-content style=\"fixed-case\">NGS<\/jats:styled-content> read coverage below app. 100.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> was extracted from peripheral blood leukocytes, and buccal swabs. The coding region, exon\u2013intron boundaries, and the flanking sequences of the genes were sequenced by <jats:styled-content style=\"fixed-case\">NGS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The proband had clinical <jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content> fulfilling the Cura\u00e7ao criteria and genetic testing identified a frameshift mutation in <jats:italic><jats:styled-content style=\"fixed-case\">ENG<\/jats:styled-content><\/jats:italic>. The mother of the proband, also with clinical <jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content>, was found negative when analyzing <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> from blood for the familial mutation using Sanger sequencing. Analyzing her <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> by <jats:styled-content style=\"fixed-case\">NGS HHT<\/jats:styled-content> panel sequencing when extracted from both peripheral blood leukocytes, and cheek swabs, identified the familial <jats:italic><jats:styled-content style=\"fixed-case\">ENG<\/jats:styled-content><\/jats:italic> mutation at low levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We provide evidence of <jats:italic><jats:styled-content style=\"fixed-case\">ENG<\/jats:styled-content><\/jats:italic> mutational mosaicism in an individual presenting with clinical <jats:styled-content style=\"fixed-case\">HHT<\/jats:styled-content>. These findings illustrate the importance of considering mutational mosaicism.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.361","type":"journal-article","created":{"date-parts":[[2017,12,15]],"date-time":"2017-12-15T01:24:37Z","timestamp":1513301077000},"page":"121-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<i><scp>ENG<\/scp><\/i> mutational mosaicism in a family with hereditary hemorrhagic telangiectasia"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7303-7619","authenticated-orcid":false,"given":"Pernille M.","family":"T\u00f8rring","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anette D.","family":"Kjeldsen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian Bomme","family":"Ousager","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Brusgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.088286"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2015.03.013"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03860.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01727.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.069013"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15732-2"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.041517"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.2000.00725.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.088112"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2011.10.036"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01596.x"},{"key":"e_1_2_7_13_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_7_14_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/cge.12269","article-title":"National mutation study among Danish patients with Hereditary Haemorrhagic Telangiectasia","volume":"86","author":"Torring P. 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