{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:21:08Z","timestamp":1747146068381,"version":"3.40.5"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"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":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Loeys\u2010Dietz syndrome (LDS), a connective tissue disorder characterized by its vascular, skeletal, craniofacial, and cutaneous manifestations is caused by mutations in one of six genes (<jats:italic>TGFBR1<\/jats:italic>, <jats:italic>TGFBR2<\/jats:italic>, <jats:italic>SMAD2<\/jats:italic>, <jats:italic>SMAD3<\/jats:italic>, <jats:italic>TGFB2<\/jats:italic>, and <jats:italic>TGFB3<\/jats:italic>). Until recently, all reported cases of LDS have been attributed to heterozygous pathogenic variants in these genes. Here, we report the first case of Loeys\u2010Dietz syndrome due to <jats:italic>SMAD3<\/jats:italic> biallelic likely pathogenic variants in a 15\u2010year\u2010old male with classic Loeys\u2010Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected. To our knowledge, this represents the first reported case of biallelic <jats:italic>SMAD3<\/jats:italic>\u2010related Loeys\u2010Dietz syndrome and the third case in the literature of biallelic LDS, indicating that there are multiple genetic modes of inheritance underlying this disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.61844","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T09:14:03Z","timestamp":1601198043000},"page":"2755-2760","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The first reported case of <scp>Loeys\u2010Dietz<\/scp> syndrome in a patient with biallelic <scp><i>SMAD3<\/i><\/scp> variants"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7148-4669","authenticated-orcid":false,"given":"Stephanie M.","family":"Baskin","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Texas Health Science at Houston  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8056-0934","authenticated-orcid":false,"given":"Shaine A.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Texas Children's Hospital and Baylor College of Medicine  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Autumn","family":"Vara","sequence":"additional","affiliation":[{"name":"UTHealth Graduate School of Biomedical Sciences The University of Texas  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline T.","family":"Hecht","sequence":"additional","affiliation":[{"name":"Department of Pediatrics McGovern Medical School and School of Dentistry UT Health at Houston  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-7490","authenticated-orcid":false,"given":"Laura S.","family":"Farach","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Texas Health Science at Houston  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-018-0444-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.01.040"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2348"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1132"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.I.01140"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/591516"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0472-7"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105583"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001485"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.744"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10145"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2349"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1511"},{"issue":"8","key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1056\/NEJMoa055695","article-title":"Aneurysm syndromes caused by mutations in the TGF\u2010beta receptor","volume":"335","author":"Loeys B. 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