{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T19:20:22Z","timestamp":1790450422562,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:00:00Z","timestamp":1616716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this retrospective single\u2010center study, we evaluated whether\/how pathogenic\/likely pathogenic variants of three hereditary hemorrhagic telangiectasia (HHT)\u2013associated genes (<jats:italic>ENG<\/jats:italic>, <jats:italic>ACVRL1<\/jats:italic>, and <jats:italic>SMAD4<\/jats:italic>) are associated with specific clinical presentations of HHT. We also characterized the morphological features of pulmonary arteriovenous malformations (AVMs) in patients with these variants. Pathogenic or likely pathogenic variants were detected in 64 patients. Using nonparametric statistical tests, we compared the type and prevalence of specific HHT diagnostic features associated with these three variants. Pathogenic variants in these genes resulted in gene\u2010specific HHT clinical presentations. Epistaxis was present in 93%, 94%, and 100% of patients with <jats:italic>ENG<\/jats:italic>, <jats:italic>ACVRL1<\/jats:italic>, and <jats:italic>SMAD4<\/jats:italic> variants, respectively (<jats:italic>p\u2009=<\/jats:italic>\u00a00.79). Pulmonary AVMs were more common in patients with the <jats:italic>ENG<\/jats:italic> variant (<jats:italic>p\u2009=<\/jats:italic>\u00a00.034) compared with other subgroups. <jats:italic>ACVRL1<\/jats:italic> variant was associated with the lowest frequency of pulmonary AVMs (<jats:italic>p\u2009=<\/jats:italic>\u00a00.034) but the highest frequency of hepatic AVMs (<jats:italic>p\u2009=<\/jats:italic>\u00a00.015). Patients with the <jats:italic>ACVRL1<\/jats:italic> variant did not have significantly more pancreatic AVMs compared with the other groups (<jats:italic>p\u2009=<\/jats:italic>\u00a00.72). <jats:italic>ENG<\/jats:italic>, <jats:italic>ACVRL1<\/jats:italic>, and <jats:italic>SMAD4<\/jats:italic> pathogenic or likely pathogenic variants are associated with gene\u2010specific HHT presentations, which is consistent with results from other HHT centers.<\/jats:p>","DOI":"10.1002\/ajmg.a.62193","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T08:21:40Z","timestamp":1616746900000},"page":"1981-1990","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical and molecular characterization of patients with hereditary hemorrhagic telangiectasia: Experience from an <scp>HHT<\/scp> Center of Excellence"],"prefix":"10.1002","volume":"185","author":[{"given":"Muhammad A.","family":"Latif","sequence":"first","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Epidemiology and Biostatistics Johns Hopkins University Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5228-5613","authenticated-orcid":false,"given":"Nara Lygia D.","family":"Sobreira","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine McKusick\u2010Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey S.","family":"Guthrie","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine McKusick\u2010Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Motaghi","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Epidemiology and Biostatistics Johns Hopkins University Bloomberg School of Public Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Shafaat","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna J.","family":"Gong","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2180-1731","authenticated-orcid":false,"given":"Clifford R.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology The Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31101"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.8.585"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20342"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/379793"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.069013"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(04)15732-2"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/hgv.2015.40"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.12.1907"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-189"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/03009734.2018.1483452"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/gim.0b013e31802d8373"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.035451"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980319)76:3<269::AID-AJMG12>3.0.CO;2-F"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-345"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3182136d32"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.55.7.959"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.160"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.12112"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.377"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22431"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.5021\/ad.2016.28.2.264"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-8628(20000306)91:1"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejm200108023450503"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.169.3.3186989"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.07.004"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62193","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62193","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:42:34Z","timestamp":1692952954000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,26]]},"references-count":28,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/ajmg.a.62193"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62193","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,26]]},"assertion":[{"value":"2020-09-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}