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The study targets the genetic basis of BAV and its complications using high-throughput sequencing and segregation analysis. Fifty-two Italian patients were analyzed, with screening of relatives for variants. Results identified rare variants across 63 genes, including NOTCH1, FBN1, GATA5, and potential roles of PDIA2, LRP1, CAPN2, MYLK, VHL, AGGF1.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/bicuspid-aortic-valve-old-and-novel-gene-contribution-to-disease-onset-and-complications/465040/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/bicuspid-aortic-valve-old-and-novel-gene-contribution-to-disease-onset-and-complications/465040.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the study aim regarding bicuspid aortic valve (BAV)?","Question",{"text":112,"@type":113},"To unravel the genetic basis of BAV and its complications, including the genetic contribution to disease onset and progression, using high-throughput sequencing and segregation analysis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were patients and relatives analyzed in the study?",{"text":117,"@type":113},"Fifty-two Italian BAV patients underwent targeted high-throughput sequencing of 97 genes, and 35 first-degree relatives of 10 probands were screened for variants found in the index cases.",{"name":119,"@type":110,"acceptedAnswer":120},"Which genetic findings were highlighted in the results?",{"text":121,"@type":113},"The study reported rare variants across 63 genes, including previously reported NOTCH1, FBN1, and GATA5 variants, and suggested additional contributions involving PDIA2, LRP1, CAPN2, as well as links to complications such as MYLK, CAPN2, VHL, and AGGF1.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},465040,1790884143,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Article  \nBicuspid Aortic Valve: Old and Novel Gene Contribution to Disease Onset and Complications  \nElena Sticchi 1,2,3, *, Rosina De Cario 1, Samuele Suraci 1, Ada Kura 1, Martina Berteotti 1,2,3, Lapo Squillantini 1, Giulia Barbieri 1, Rebecca Orsi 1, Maria Pia Fugazzaro 4, Stefania Colonna 5,  \nFrancesca Gensini 6, Erika Fiorentini 6, Anna Maria Gori 1,2,3, Rossella Marcucci 1,2,3, Guglielmina Pepe 1, Stefano Nistri 4 and Betti Giusti 1,2,3  \nAcademic Editor: Elad Asher  \nReceived: 17 November 2025  \nRevised: 13 December 2025  \nAccepted: 14 December 2025  \nPublished: 28 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy; decariorosy@hotmail.it (R.D.C.); samuele.suraci@unifi.it (S.S.); ada.kura@unifi.it (A.K.);  \nmartina.berteotti@unifi.it (M.B.); l.squillantini@student.unisi.it (L.S.); giulia.barbieri@unifi.it (G.B.);  \nr.orsi2@student.unisi.it (R.O.); annamaria.gori@unifi.it (A.M.G.); rossella.marcucci@unifi.it (R.M.);  \n[guglielminapepe@hotmail.it](guglielminapepe@hotmail.it) (G.P.); [betti.giusti@unifi.it](betti.giusti@unifi.it) (B.G.)  \n2 Marfan Syndrome and Related Disorders Regional (Tuscany) Referral Center, Careggi Hospital,  \n50139 Florence, Italy  \n3 Atherothrombotic Diseases Center, Cardiothoracovascular Department, Careggi University Hospital,  \n50134 Florence, Italy  \n4 Cardiology Service, CMSR Veneto Medica, 36077 Altavilla Vicentina, Italy;  \n[mariapiafugazzaro@hotmail.it](mariapiafugazzaro@hotmail.it) (M.P.F.); [stefanonistri41@gmail.com](stefanonistri41@gmail.com) (S.N.)  \n5 Outpatient Cardiology Unit, Health District 1 ULSS 6, Vigonza and Carmignano di Brenta, 35128 Padua, Italy; [stefaniacolonna@hotmail.com](stefaniacolonna@hotmail.com)  \n6 Medical Genetics Unit, Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio’, University of Florence, 50139 Florence, Italy; francesca.gensini@unifi.it (F.G.); erika.fiorentini@unifi.it (E.F.)  \n* [Correspondence: elena.sticchi@unifi.it](Correspondence: elena.sticchi@unifi.it); Tel.: +39-0557948913 (ext. 8906)  \nAbstract  \nBackground: Bicuspid aortic valve (BAV) is the most common congenital heart defect, and its complications (namely, dilatation of the thoracic ascending aorta) raise concerns regarding the proper timing of aortic surgery. The study aim is to unravel the genetic basis of BAV and its complications through a high-throughput sequencing (HTS) approach and segregation analysis if family members were available. Methods: Fifty-two Italian BAV patients were analyzed by HTS using the Illumina MiSeq platform. Targeted sequencing of 97 genes known to be or plausibly associated with connective tissue disorders or aorthopathy was performed. Thirty-five first-degree relatives of N = 10 probands underwent mutational screening for variants identified in the index cases. Results: HTS identified 194 rare (MAF \u003C 0.01) variants in 63 genes. Regarding previously reported genes, five NOTCH1 variants in four BAV patients, four FBN1 variants in two patients and one GATA5 variant in one patient were identified. Interestingly, among further loci, the possible contribution of PDIA2, LRP1 and CAPN2 was suggested by (a) the increased prevalence of rare genetic variants, independently from their ACMG classification in the whole BAV cohort, and (b) segregation analyses of variants identified in family members. Moreover, the present data also suggest the possible contribution of rare variants to BAV complications, specifically MYLK in aortic dilatation, CAPN2 in BAV calcification and VHL and AGGF1 in valve stenosis. Conclusions: Our results underline clinical and genetic diagnosis complexity in traits considered monogenic, such as BAV, but characterized by variability in disease ","cbCairlnzUg2itxw","https://ap.wps.com/l/cbCairlnzUg2itxw","pdf",984950,17,"English","# Abstract\n# 1. Introduction","[{\"question\":\"What was the study aim regarding bicuspid aortic valve (BAV)?\",\"answer\":\"To unravel the genetic basis of BAV and its complications, including the genetic contribution to disease onset and progression, using high-throughput sequencing and segregation analysis.\"},{\"question\":\"How were patients and relatives analyzed in the study?\",\"answer\":\"Fifty-two Italian BAV patients underwent targeted high-throughput sequencing of 97 genes, and 35 first-degree relatives of 10 probands were screened for variants found in the index cases.\"},{\"question\":\"Which genetic findings were highlighted in the results?\",\"answer\":\"The study reported rare variants across 63 genes, including previously reported NOTCH1, FBN1, and GATA5 variants, and suggested additional contributions involving PDIA2, LRP1, CAPN2, as well as links to complications such as MYLK, CAPN2, VHL, and AGGF1.\"}]","Bicuspid Aortic Valve - Old and Novel Gene Contribution to Disease Onset and Complications | PDF",1790769084,43]