{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:41:21Z","timestamp":1787992881058,"version":"build-2784847793"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL109942"],"award-info":[{"award-number":["R01HL109942"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Exome sequencing of genes associated with heritable thoracic aortic disease (HTAD) failed to identify a pathogenic variant in a large family with Marfan syndrome (MFS). A genome\u2010wide linkage analysis for thoracic aortic disease identified a peak at 15q21.1, and genome sequencing identified a novel deep intronic\n                    <jats:italic>FBN1<\/jats:italic>\n                    variant that segregated with thoracic aortic disease in the family (LOD score 2.7) and was predicted to alter splicing. RT\u2010PCR and bulk RNA sequencing of RNA harvested from fibroblasts explanted from the affected proband revealed an insertion of a pseudoexon between exons 13 and 14 of the\n                    <jats:italic>FBN1<\/jats:italic>\n                    transcript, predicted to lead to nonsense mediated decay (NMD). Treating the fibroblasts with an NMD inhibitor, cycloheximide, greatly improved the detection of the pseudoexon\u2010containing transcript. Family members with the\n                    <jats:italic>FBN1<\/jats:italic>\n                    variant had later onset aortic events and fewer MFS systemic features than typical for individuals with haploinsufficiency of\n                    <jats:italic>FBN1<\/jats:italic>\n                    . Variable penetrance of the phenotype and negative genetic testing in MFS families should raise the possibility of deep intronic\n                    <jats:italic>FBN1<\/jats:italic>\n                    variants and the need for additional molecular studies.\n                  <\/jats:p>","DOI":"10.1111\/cge.14322","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T03:57:00Z","timestamp":1677729420000},"page":"704-708","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["An\n                    <i>FBN1<\/i>\n                    deep intronic variant is associated with pseudoexon formation and a variable Marfan phenotype in a five generation family"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7402-3104","authenticated-orcid":false,"given":"Dong\u2010chuan","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Mimnagh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine WVU School of Medicine\u2010Charleston Division (Retired)  Morgantown West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9588-8705","authenticated-orcid":false,"given":"Alana C.","family":"Cecchi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella C.","family":"Marin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter V.","family":"Velasco","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwanghyuk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8536-3091","authenticated-orcid":false,"given":"David R.","family":"Murdock","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Leal","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsha M.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Genome Sciences University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Smith","sequence":"additional","affiliation":[{"name":"Genome Sciences University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Bamshad","sequence":"additional","affiliation":[{"name":"Genome Sciences University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7806-0068","authenticated-orcid":false,"given":"Dianna M.","family":"Milewicz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Texas Health Science Center at Houston (UTHealth)  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101228"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21525"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20070"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22540"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-008-0334-7"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2020.02.032"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141500"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.072785"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010020\u201001078\u20106"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001132\u2010x"}],"container-title":["Clinical 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