{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T09:31:14Z","timestamp":1759483874525,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Marfan syndrome (MFS) is a hereditary connective tissue disorder involving multiple systems, including ophthalmologic abnormalities. Most cases are due to heterozygous mutations in the fibrillin\u20101 gene (FBN1). Other associated genes include LTBP2, MYH11, MYLK, and SLC2A10. There is significant clinical overlap between MFS and other Marfan\u2010like disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To expand the mutation spectrum of <jats:italic>FBN1<\/jats:italic> gene and validate the pathogenicity of Marfan\u2010related genes in patients with MFS and ocular manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 318 participants (195 cases, 123 controls), including 59 sporadic cases and 88 families. All patients had comprehensive ophthalmic examinations showing ocular features of MFS and met Ghent criteria. Additionally, 754 cases with other eye diseases were recruited. Panel\u2010based next\u2010generation sequencing (NGS) screened mutations in 792 genes related to inherited eye diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected 181 mutations with an 84.7% detection rate in sporadic cases and 87.5% in familial cases. The overall detection rate was 86.4%, with FBN1 accounting for 74.8%. In cases without FBN1 mutations, 23 mutations from seven Marfan\u2010related genes were identified, including four pathogenic or likely pathogenic mutations in LTBP2. The 181 mutations included 165 missenses, 10 splicings, three frameshifts, and three nonsenses. FBN1 accounted for 53.0% of mutations. The most prevalent pathogenic mutation was FBN1 c.4096G&gt;A. Additionally, 94 novel mutations were detected, with 13 de novo mutations in 14 families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We expanded the mutation spectrum of the FBN1 gene and provided evidence for the pathogenicity of other Marfan\u2010related genes. Variants in LTBP2 may contribute to the ocular manifestations in MFS, underscoring its role in phenotypic diversity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2482","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T10:46:27Z","timestamp":1720003587000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted next\u2010generation sequencing reveals the genetic mechanism of Chinese Marfan syndrome cohort with ocular manifestation"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5622-2042","authenticated-orcid":false,"given":"Dongming","family":"Han","sequence":"first","affiliation":[{"name":"College of Life Sciences University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziwei","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Sciences University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijia","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Sciences University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengtao","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Biology and Biological Engineering South China University of Technology  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyi","family":"Tian","sequence":"additional","affiliation":[{"name":"College of Life Sciences University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiankang","family":"Li","sequence":"additional","affiliation":[{"name":"City University of Hong Kong Shenzhen Research Institute  Shenzhen China"},{"name":"He University  Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZhuoShi","family":"Wang","sequence":"additional","affiliation":[{"name":"He University  Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)86449-9"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.5603\/CJ.2013.0066"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.01.040"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.5435\/JAAOS-D-16-00143"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.52.4.651"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.28.4.267"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.12.7745"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.002"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.1.34"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(92)90202-4"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2349"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1511"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-024-01822-w"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31552"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.11.3.321"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1392"},{"issue":"6","key":"e_1_2_12_18_1","first-page":"888","article-title":"Diagnosis and management of infantile marfan syndrome","volume":"86","author":"Morse R. 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