{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:53:35Z","timestamp":1753869215505,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by pathogenic variants of the fibrillin\u20101\u2010encoding <jats:italic>FBN1<\/jats:italic> gene that commonly affects the cardiovascular, skeletal, and ocular systems. This study aimed to evaluate the clinical features and genetic causes of the MFS phenotype in a large Iranian family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventeen affected family members were examined clinically by cardiologists and ophthalmologists. The proband, a 48\u2010year\u2010old woman with obvious signs of MFS, her DNA sample subjected to whole\u2010exome sequencing (WES). The candidate variant was validated by bidirectional sequencing of proband and other available family members. In silico analysis and molecular modeling were conducted to determine the pathogenic effects of the candidate variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The most frequent cardiac complications are mitral valve prolapse and regurgitation. Ophthalmic examination revealed iridodonesis and ectopic lentis. A heterozygous missense variant (c.2179T&gt;C\/p.C727R) in exon 19 of <jats:italic>FBN1<\/jats:italic> gene was identified and found to cosegregate with affected family members. Its pathogenicity has been predicted using several in silico predictive algorithms. Molecular docking analysis indicated that the variant might affect the binding affinity between FBN1 and LTBP1 proteins by impairing disulfide bond formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our report expands the spectrum of the Marfan phenotype by providing details of its clinical manifestations and disease\u2010associated molecular changes. It also highlights the value of WES in genetic diagnosis and contributes to genetic counseling in families with MFS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hsr2.1647","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T12:39:41Z","timestamp":1698064781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case study"],"prefix":"10.1002","volume":"6","author":[{"given":"Farzane","family":"Vafaeie","sequence":"first","affiliation":[{"name":"Cellular and Molecular Research Center Birjand University of Medical Sciences Birjand Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zahra","family":"Miri Karam","sequence":"additional","affiliation":[{"name":"Physiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman Iran"},{"name":"Department of Medical Genetics, Afzalipour Faculty of Medicine Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abolfazl","family":"Yari","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Research Center Birjand University of Medical Sciences Birjand Iran"},{"name":"Department of Medical Genetics, Afzalipour Faculty of Medicine Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossein","family":"Safarpour","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Research Center Birjand University of Medical Sciences Birjand Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tooba","family":"Kazemi","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Research Center, Razi Hospital Birjand University of Medical Sciences Birjand Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shokoofeh","family":"Etesam","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Technical and Vocational University (TVU) Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mojtaba","family":"Mohammadpour","sequence":"additional","affiliation":[{"name":"Department of Optometry, School of Rehabilitation Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9435-2450","authenticated-orcid":false,"given":"Ebrahim","family":"Miri\u2010Moghaddam","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Research Center, Razi Hospital Birjand University of Medical Sciences Birjand Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11050574"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/514346"},{"volume-title":"Genetics, Clinical Features, and Diagnosis of Marfan Syndrome and Related Disorders","year":"2020","author":"Wright M","key":"e_1_2_12_4_1"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01646.x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12358"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2016.07.033"},{"key":"e_1_2_12_8_1","article-title":"Genotype\u2010phenotype correlations of Marfan syndrome and related fibrillinopathies: phenomenon and molecular relevance","volume":"13","author":"Chen ZX","year":"2022","journal-title":"Front Genet [Internet]"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-80614-9_4"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24383"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.072785"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_12_13_1","unstructured":"AndrewsS.Babraham bioinformatics. 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