{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:42:12Z","timestamp":1790260932620,"version":"4.1.0"},"reference-count":28,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2011,2,5]]},"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder affecting the vascular system, characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. Mutations in two genes, <jats:italic>ENG<\/jats:italic> and <jats:italic>ACVRL1<\/jats:italic>, account for the majority of cases. Almost all cases of HHT show a family history of HHT-associated symptoms; few cases are de novo. Mutational mosaicism is the presence of two populations of cells, with both mutant and normal genotypes in one individual and generally occurs through de novo mutation events in embryogenesis. Some isolated cases of HHT with no detectable <jats:italic>ENG<\/jats:italic> or <jats:italic>ACVRL1<\/jats:italic> mutation may be caused by a mosaic <jats:italic>ENG<\/jats:italic> or <jats:italic>ACVRL1<\/jats:italic> mutation that is present at levels below the limit of detection of current molecular screening methods.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To identify clinically relevant mosaicism in type I HHT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Sequencing, quantitative multiplex-PCR and marker analysis were used to identify three HHT families with founders who showed mosaicism for endoglin mutations. Where available, mosaicism was verified by testing different sampling sites, including blood, hair and buccal swabs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All three mosaic samples exhibited the mutation in an estimated \u226425% of the DNA. Two of the mosaic patients had clinically confirmed HHT by the Cura\u00e7ao criteria and the other showed symptoms of HHT. In each case the heterozygous mutation had already been identified in another family member before detection in the mosaic founder.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The results show the importance of investigating patients without prior family history for the presence of mutational mosaicism, as detecting this would enable appropriate genetic screening and targeted medical care for at-risk children of mosaic patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2010.088112","type":"journal-article","created":{"date-parts":[[2011,3,17]],"date-time":"2011-03-17T23:07:41Z","timestamp":1300403261000},"page":"353-357","source":"Crossref","is-referenced-by-count":17,"title":["Identification of clinically relevant mosaicism in type I hereditary haemorrhagic telangiectasia"],"prefix":"10.1136","volume":"48","author":[{"given":"Nadia Prigoda","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donco","family":"Matevski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Dumitru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Piovesan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Rushlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda L","family":"Gallie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2011,3,17]]},"reference":[{"key":"2025101712410092000_48.5.353.1","first-page":"1322","article-title":"\u00c3\u0089pistaxis r\u00c3\u00a9p\u00c3\u00a9t\u00c3\u00a9es chez un sujet porteur de petits angiomes cutan\u00c3\u00a9s et muqueux","volume":"135","author":"Rendu","year":"1896","journal-title":"Gaz Hop Paris"},{"key":"2025101712410092000_48.5.353.2","first-page":"333","article-title":"On a family form of recurring epistaxis associated with multiple telangiectases of the skin and mucous membrane","volume":"12","author":"Osler","year":"1901","journal-title":"Bull Johns Hopkins Hosp"},{"key":"2025101712410092000_48.5.353.3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.042606"},{"key":"2025101712410092000_48.5.353.4","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000306)91:1<66::AID-AJMG12>3.0.CO;2-P"},{"key":"2025101712410092000_48.5.353.5","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.069013"},{"key":"2025101712410092000_48.5.353.6","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20342"},{"key":"2025101712410092000_48.5.353.7","unstructured":"ARUP's laboratory test directory. Hereditary hemorrhagic telangiectasia (ACVRL1 and ENG) sequencing & deletion\/duplication: 0051382. http:\/\/www.aruplab.com\/guides\/ug\/tests\/0051382.jsp (accessed 24 Jan 2011)."},{"key":"2025101712410092000_48.5.353.8","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028712"},{"key":"2025101712410092000_48.5.353.9","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1002\/ajmg.a.31450","article-title":"A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7","volume":"140","author":"Bayrak-Toydemir","year":"2006","journal-title":"Am J Med Genet A"},{"key":"2025101712410092000_48.5.353.10","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0031-3955(16)38298-0","article-title":"Nontraditional inheritance","volume":"39","author":"Austin","year":"1992","journal-title":"Pediatr Clin North Am"},{"key":"2025101712410092000_48.5.353.11","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050708"},{"key":"2025101712410092000_48.5.353.12","doi-asserted-by":"publisher","DOI":"10.1038\/nrg906"},{"key":"2025101712410092000_48.5.353.13","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1111\/j.1582-4934.2007.00122.x","article-title":"Mosaicism in von Hippel-Lindau disease: an event important to recognize","volume":"11","author":"Santarpia","year":"2007","journal-title":"J Cell Mol Med"},{"key":"2025101712410092000_48.5.353.14","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20940"},{"key":"2025101712410092000_48.5.353.15","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh134"},{"key":"2025101712410092000_48.5.353.16","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.13.2051"},{"key":"2025101712410092000_48.5.353.17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903043400905"},{"key":"2025101712410092000_48.5.353.18","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10203"},{"key":"2025101712410092000_48.5.353.19","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.10.721"},{"key":"2025101712410092000_48.5.353.20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30465"},{"key":"2025101712410092000_48.5.353.21","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.10.816"},{"key":"2025101712410092000_48.5.353.22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa013452"},{"key":"2025101712410092000_48.5.353.23","doi-asserted-by":"publisher","DOI":"10.1016\/0270-9139(93)90133-8"},{"key":"2025101712410092000_48.5.353.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2009.11.006"},{"key":"2025101712410092000_48.5.353.25","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-007-0187-5"},{"key":"2025101712410092000_48.5.353.26","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/GIM.0b013e31802d8373","article-title":"Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data from the French-Italian HHT network","volume":"9","author":"Lesca","year":"2007","journal-title":"Genet Med"},{"key":"2025101712410092000_48.5.353.27","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.8.585"},{"key":"2025101712410092000_48.5.353.28","doi-asserted-by":"publisher","DOI":"10.1080\/00016480802468138"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.2010.088112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:41:08Z","timestamp":1760730068000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.2010.088112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,17]]},"references-count":28,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2011,4,27]]},"published-print":{"date-parts":[[2011,5]]}},"alternative-id":["10.1136\/jmg.2010.088112"],"URL":"https:\/\/doi.org\/10.1136\/jmg.2010.088112","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,17]]}}}