{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T09:11:04Z","timestamp":1772269864454,"version":"3.50.1"},"reference-count":28,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"crossref","award":["BK20151590"],"award-info":[{"award-number":["BK20151590"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine)"},{"name":"Top-notch Academic Programs Project of Jiangsu Higher Education Institutions","award":["PPZY2015A067"],"award-info":[{"award-number":["PPZY2015A067"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Marfan syndrome (MFS) is an inherited connective tissue disorder affecting the ocular, skeletal and cardiovascular systems. Previous studies of MFS have demonstrated the association between genetic defects and clinical manifestations. Our purpose was to investigate the role of novel genetic variants in determining MFS clinical phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We sequenced the whole exome of 19 individuals derived from three Han Chinese families. The sequencing data were analyzed by a standard pipeline. Variants were further filtered against the public database and an in-house database. Then, we performed pedigree analysis under different inheritance patterns according to American College of Medical Genetics guidelines. Results were confirmed by Sanger sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two novel loss-of-function indels (c.5027_5028insTGTCCTCC, p.D1677Vfs*8; c.5856delG, p.S1953Lfs*27) and one nonsense variant (c.8034C&gt;A, p.Y2678*) of\n                      <jats:italic>FBN1<\/jats:italic>\n                      were identified in Family 1, Family 2 and Family 3, respectively. All affected members carried pathogenic mutations, whereas other unaffected family members or control individuals did not. These different kinds of loss of function (LOF) variants of\n                      <jats:italic>FBN1<\/jats:italic>\n                      were located in the cbEGF region and a conserved domain across species and were not reported previously.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study extended and strengthened the vital role of\n                      <jats:italic>FBN1<\/jats:italic>\n                      LOF mutations in the pathogenesis of MFS with an autosomal dominant inheritance pattern. We confirm that genetic testing by next-generation sequencing of blood DNA can be fundamental in helping clinicians conduct mutation-based pre- and postnatal screening, genetic diagnosis and clinical management for MFS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.5927","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T03:50:41Z","timestamp":1542081041000},"page":"e5927","source":"Crossref","is-referenced-by-count":6,"title":["Family-based whole-exome sequencing identifies novel loss-of-function mutations of\n                    <i>FBN1<\/i>\n                    for Marfan syndrome"],"prefix":"10.7717","volume":"6","author":[{"given":"Zhening","family":"Pu","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China"},{"name":"State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China"},{"name":"Center of Clinical Research, Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi, Jiangsu, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoliang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China"},{"name":"State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keshuai","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Buqing","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weidong","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juncheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China"},{"name":"State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongfeng","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"issue":"1","key":"10.7717\/peerj.5927\/ref-1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1002\/humu.9207","article-title":"Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a related fibrillinopathy","volume":"23","author":"Biggin","year":"2004","journal-title":"Human Mutation"},{"issue":"1","key":"10.7717\/peerj.5927\/ref-2","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.mayocp.2013.08.022","article-title":"Epidemiological profile of 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