{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:17:55Z","timestamp":1783012675465,"version":"3.54.6"},"reference-count":8,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Characterization of the molecular basis of connective tissue disorders causing aortopathy is important for clinical management. We report a 4\u2010generation family with autosomal dominant inheritance of a connective tissue disorder causing aortic dilatation and\/or dissection. Linkage analysis performed in the 1990s had suggested Marfan syndrome, but the molecular basis proved elusive over two decades. Reanalysis of genome sequence data using software to detect copy number variation (CNV) identified a 19\u2009kb deletion including the final exon of\n                    <jats:italic>TGFB2<\/jats:italic>\n                    , revealing Loeys\u2010Dietz syndrome type 4 as the actual diagnosis. This allowed predictive testing of at\u2010risk relatives and appropriate screening of affected patients. Small genomic deletions are difficult to detect on microarray and standard sequencing platforms, and the report highlights the role of high\u2010resolution CNV detection in molecular diagnostics.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70130","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:50:47Z","timestamp":1773805847000},"page":"1842-1845","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Refinement of Connective Tissue Disorder Diagnosis From Marfan to Loeys\u2010Dietz Syndrome Type 4\u2014End of a 30\u2010Year Diagnostic Odyssey"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6138-1386","authenticated-orcid":false,"given":"Neel","family":"Kothari","sequence":"first","affiliation":[{"name":"Cardiology New Cross Hospital  Wolverhampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Shannon","sequence":"additional","affiliation":[{"name":"Clinical Genetics Nottingham University Hospitals  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bara","family":"Erhayiem","sequence":"additional","affiliation":[{"name":"Cardiology Nottingham University Hospitals  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohnish","family":"Suri","sequence":"additional","affiliation":[{"name":"Clinical Genetics Nottingham University Hospitals  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair T.","family":"Pagnamenta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences University of Exeter  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Dixit","sequence":"additional","affiliation":[{"name":"Clinical Genetics Nottingham University Hospitals  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2348"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61633"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol\u20102017\u2010311254"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62758"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001106"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2349"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12101462"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","unstructured":"Yu J. A.Szabo A. T.Pagnamenta et\u00a0al.2021.\u201cSVRare: Discovering Disease\u2010Causing Structural Variants in the 100K Genomes Project \u201dmedRxiv.https:\/\/doi.org\/10.1101\/2021.10.15.21265069.","DOI":"10.1101\/2021.10.15.21265069"}],"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.70130","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70130","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70130","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:29:30Z","timestamp":1783009770000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":8,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ajmg.a.70130"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70130","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]},"assertion":[{"value":"2025-10-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}