{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:02:14Z","timestamp":1780635734456,"version":"3.54.1"},"reference-count":97,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015773","name":"Instituto Nacional de Cardiologia Ignacio Chavez","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015773","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Marfan syndrome (MS), Loeys\u2013Dietz syndrome (LDS), Beals\u2013Hecht syndrome (BHS), Ehlers\u2013Danlos syndrome (EDS), and individuals with undifferentiated connective tissue disease (UCTD) exhibit phenotypic overlap, suggesting a likelihood of genotypic coexistence. Our objective was to evaluate genetic variants (GVs), encoding 174 genes related to aortopathies, cardiomyopathies, arrhythmias, structural heart disease, and hypercholesterolemia, and their relationship to clinical and cardiovascular damage in these syndromes. This was a prospective study in Mexican patients with MS, LDS, EDS, BHS, and UCTD. One hundred and seventy-four genes related to hereditary diseases were studied using next-generation sequencing targeting coding regions. Of the 136 patients, 25 were identified with the recurrent and coexisting GV of MYBPC3. In the MS group, in addition to the presence of GV in FBN1, eight patients had GV in MYBPC3, six in FBN2, and five in COL3A1 and COL5A1. In the LDS group, in addition to GV in TGFBR1, TGFBR2, and SMAD3, four patients presented with GV in MYBPC3 and two with FBN2. In the BHS group, in addition to FBN2, two patients had GV in MYBPC3 and one with TGFBR2. In the UCTD group, nine patients had GV in MYBPC3 and two in COL5A1 and COL5A2. All syndromes coexisted with GV in genes related to arrhythmias, sarcomeres, and hypercholesterolemia. In EDS, coexistence with several sarcomere proteins was found.<\/jats:p>","DOI":"10.3390\/cells15111001","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:57:18Z","timestamp":1780070238000},"page":"1001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular and Clinical Manifestations of Marfan Syndrome and Other Inherited Connective Tissue Disorders with Coexisting Genetic Variants"],"prefix":"10.3390","volume":"15","author":[{"given":"Maria Elena","family":"Soto","sequence":"first","affiliation":[{"name":"Research Direction, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"},{"name":"Cardiovascular Line in American British Cowdray (ABC) Medical Center, PAI ABC Sur 136 No. 116, Col. Las America\u2019s, M\u00e9xico City 01120, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7916-5163","authenticated-orcid":false,"given":"Gilberto","family":"Vargas-Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Research Direction, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6806-3484","authenticated-orcid":false,"given":"Claudia","family":"Huesca-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Physiology Department, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-2954","authenticated-orcid":false,"given":"Israel","family":"P\u00e9rez-Torres","sequence":"additional","affiliation":[{"name":"Cardiovascular Biomedicine Department, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Ba-diano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Arias-God\u00ednez","sequence":"additional","affiliation":[{"name":"Echocardiography Department, Instituto Nacional de Cardiologia Ignacio Ch\u00e1vez Juan Badiano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio Enrique","family":"Meza-Toledo","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional (IPN), Manuel Carpio y Plutarco Elias Calles, Col. Miguel Hidalgo, M\u00e9xico City 11350, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6493-7765","authenticated-orcid":false,"given":"Regina de la","family":"Mora-Cervantes","sequence":"additional","affiliation":[{"name":"Computed Tomography Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0336-5593","authenticated-orcid":false,"given":"Hugo","family":"Rodr\u00edguez-Zanella","sequence":"additional","affiliation":[{"name":"Echocardiography Department, Instituto Nacional de Cardiologia Ignacio Ch\u00e1vez Juan Badiano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Mel\u00e9ndez-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Magnetic Resonance Department, Instituto Nacional de Cardiologia Ignacio Ch\u00e1vez Juan Badiano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linaloe","family":"Manzano-Pech","sequence":"additional","affiliation":[{"name":"Cardiovascular Biomedicine Department, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Ba-diano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1819-8444","authenticated-orcid":false,"given":"Giovanny","family":"Fuentevilla-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9102-4240","authenticated-orcid":false,"given":"Ricardo","family":"Gamboa","sequence":"additional","affiliation":[{"name":"Physiology Department, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano No. 1. Col. Secci\u00f3n XVI, M\u00e9xico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","first-page":"137","article-title":"Perspectives on the revised Ghent criteria for the diagnosis of Marfan syndrome","volume":"8","author":"Bannas","year":"2015","journal-title":"Appl. Clin. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kolambage, Y.D., Cooray, A.L., Priyawansha, Y.G.T., Hendalage, D.P.B., Liyanage, U.A., and Dissanayake, V.H.W. (2025). Characterisation of Type-1 Fibrillinopathies in a Sri Lankan Cohort: Genotype-Phenotype Correlations and Novel FBN1 Variants. Mol. Syndromol., Online ahead of print.","DOI":"10.1159\/000549606"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.ijcard.2015.03.423","article-title":"Molecular pathogenesis of Marfan syndrome","volume":"187","author":"Ramachandra","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/bs.mcb.2017.08.013","article-title":"Fibrillins","volume":"143","author":"Kumra","year":"2018","journal-title":"Methods Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ajmg.c.30068","article-title":"Recent progress towards a molecular understanding of Marfan syndrome","volume":"139C","author":"Dietz","year":"2005","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1510\/icvts.2010.239681","article-title":"In search of a new therapeutic target for the treatment of genetically triggered thoracic aortic aneurysms and cardiovascular conditions: Insights from human and animal lathyrism","volume":"11","author":"Sherif","year":"2010","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.acvd.2010.04.008","article-title":"Rationale and design of a randomized clinical trial (Marfan Sartan) of angiotensin II receptor blocker therapy versus placebo in individuals with Marfan syndrome","volume":"103","author":"Detaint","year":"2010","journal-title":"Arch. Cardiovasc. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2174\/1573403X1002140506124902","article-title":"Medical treatment of aortic aneurysms in Marfan syndrome and other heritable conditions","volume":"10","author":"Greutmann","year":"2014","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/j.1365-2125.2011.03929.x","article-title":"Preventing the aortic complications of Marfan syndrome: A case-example of translational genomic medicine","volume":"72","author":"Loeys","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12967-025-07523-x","article-title":"Phenotype-driven clustering of ocular manifestations reveals prognostic and genetic heterogeneity in Marfan syndrome: A real-world longitudinal cohort study","volume":"24","author":"Shen","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"302","DOI":"10.17305\/bb.2023.9578","article-title":"The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders","volume":"24","author":"Soto","year":"2024","journal-title":"Biomol. Biomed."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(05)67789-6","article-title":"Marfan\u2019s syndrome","volume":"366","author":"Judge","year":"2005","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/humu.20070","article-title":"Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome","volume":"24","author":"Loeys","year":"2004","journal-title":"Hum. Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.mrrev.2015.04.002","article-title":"Engineered mutations in fibrillin-1 leading to Marfan syndrome act at the protein, cellular and organismal levels","volume":"765","author":"Zeyer","year":"2015","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1136\/jmg.2005.039669","article-title":"The molecular genetics of Marfan syndrome and related disorders","volume":"43","author":"Robinson","year":"2006","journal-title":"J. Med. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chalk, T., Burns, K., and Morton, A. (2025). Inherited aortopathies and risk of aortic dissection and aortic syndrome in pregnancy. Obstet. Med., 1753495X251359834.","DOI":"10.1177\/1753495X251359834"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.amjcard.2022.04.012","article-title":"Prevalence and Outcomes of Primary Left Ventricular Dysfunction in Marfan Syndrome","volume":"175","author":"Connor","year":"2022","journal-title":"Am. J. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s40292-024-00692-8","article-title":"Echocardiographic Assessment in Patients with Vascular Ehlers-Danlos Syndrome: Insights from an Unexplored Field","volume":"32","author":"Buso","year":"2025","journal-title":"High Blood Press. Cardiovasc. Prev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s003920170017","article-title":"Marfan syndrome and valvular disease","volume":"90","author":"Pasic","year":"2001","journal-title":"Z. Kardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.echo.2011.09.004","article-title":"Biventricular performance in patients with marfan syndrome without significant valvular disease: Comparison to normal subjects and longitudinal follow-up","volume":"24","author":"Scherptong","year":"2011","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.amjcard.2025.08.032","article-title":"Postoperative Outcomes and Valvular Involvement in Loeys-Dietz Syndrome: A Multicenter Cohort Study of Surgical Risk and Complications","volume":"257","author":"Nabi","year":"2025","journal-title":"Am. J. Cardiol."},{"key":"ref_22","first-page":"72","article-title":"To Repair or Replace the Mitral Valve in Ehlers-Danlos Syndrome? A Case Report","volume":"18","author":"Kavyani","year":"2023","journal-title":"J. Tehran Univ. Heart Cent."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Demolder, A., von Kodolitsch, Y., Mui\u00f1o-Mosquera, L., and De Backer, J. (2020). Myocardial Function, Heart Failure and Arrhythmia in Marfan Syndrome: A Systematic Literature Review. Diagnostics, 10.","DOI":"10.3390\/diagnostics10100751"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4103\/njcp.njcp_675_20","article-title":"Marfan Syndrome with Aortic Root Disease, Severe Heart Failure and Aortic Dissection\u2014Two Case Reports","volume":"25","author":"Njoku","year":"2022","journal-title":"Niger. J. Clin. Pract."},{"key":"ref_25","first-page":"389","article-title":"Loeys-Dietz Cardiomyopathy? Long-term Follow-up After Onset of Acute Decompensated Heart Failure","volume":"38","author":"Yokota","year":"2022","journal-title":"Can. J. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"368","DOI":"10.4330\/wjc.v12.i8.368","article-title":"Classic Ehlers-Danlos syndrome and cardiac transplantation\u2014Is there a connection?","volume":"12","author":"Butler","year":"2020","journal-title":"World J. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.jaccas.2021.08.006","article-title":"Mitral Annular Disjunction Associated with Fatal Ventricular Arrhythmia in an Adolescent with Marfan Syndrome","volume":"3","author":"Carr","year":"2021","journal-title":"JACC Case Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102269","DOI":"10.1016\/j.jacadv.2025.102269","article-title":"The Burden of Cardiac Arrhythmias in Loeys-Dietz Syndrome: Prevalence, Etiology, and Therapeutic Interventions","volume":"4","author":"Nabi","year":"2025","journal-title":"JACC Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1016\/j.ijcard.2012.06.036","article-title":"Prospective risk strati fi cation of sudden cardiac death in Marfan\u2019s syndrome","volume":"167","author":"Hoffmann","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101967","DOI":"10.1016\/j.legalmed.2021.101967","article-title":"Sudden death due to a novel nonsense mutation in Marfan syndrome","volume":"53","author":"Zhao","year":"2021","journal-title":"Leg. Med."},{"key":"ref_31","first-page":"85","article-title":"Sudden cardiac death in young athletes","volume":"2","year":"2011","journal-title":"Open Access J. Sports Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Abu-Sailik, F., Gariballa, N., and Ali, B.R. (2025). Decoding clinical diversity in monogenic TGFBR1 and TGFBR2 mutations: Insights into the interplay of molecular mechanisms and hypomorphicity. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1580274"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1023","DOI":"10.1002\/mgg3.1023","article-title":"Genetic and molecular mechanism for distinct clinical phenotypes conveyed by allelic truncating mutations implicated in FBN1","volume":"8","author":"Lin","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1002\/ajmg.a.62905","article-title":"Next-generation sequencing and analysis of consecutive patients referred for connective tissue disorders","volume":"188","author":"Steinle","year":"2022","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Veatch, O.J., Steinle, J., Hossain, W.A., and Butler, M.G. (2022). Clinical genetics evaluation and testing of connective tissue disorders: A cross-sectional study. BMC Med. Genom., 15.","DOI":"10.1186\/s12920-022-01321-w"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/jmg.2009.072785","article-title":"The revised Ghent nosology for the Marfan syndrome","volume":"47","author":"Loeys","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/humu.22977","article-title":"Marfan Syndrome and Related Disorders: 25 Years of Gene Discovery","volume":"37","author":"Verstraeten","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Stathori, G., Koniari, E., Vlachakis, D., Papanikolaou, E., Chrousos, G.P., and Yapijakis, C. (2025). Genotype-Phenotype Correlation Insights Through Molecular Modeling Analysis in a Patient with Loeys-Dietz Syndrome. Genes, 16.","DOI":"10.3390\/genes16040357"},{"key":"ref_39","first-page":"101193","article-title":"FBN2 pathogenic mutation in congenital contractural arachnodactyly with severe skeletal manifestations","volume":"42","author":"Huang","year":"2025","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Qiu, J., Lou, Y., Zhu, Y., Wang, M., Peng, H., Hao, Y., Jiang, H., and Mao, Y. (2021). Clinical Characteristics and Genetic Analysis of a Family with Birt-Hogg-Dub\u00e9 Syndrome and Congenital Contractural Arachnodactyly. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.768342"},{"key":"ref_41","unstructured":"Callewaert, B. (1993). Congenital Contractural Arachnodactyly. GeneReviews\u00ae, University of Washington, Seattle."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/dvdy.220","article-title":"Hypermobile Ehlers-Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes","volume":"250","author":"Gensemer","year":"2021","journal-title":"Dev. Dyn."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1097\/MS9.0000000000002969","article-title":"Genetic factors and management strategies in aortic health: A literature review of inherited aortopathy","volume":"87","author":"Elendu","year":"2025","journal-title":"Ann. Med. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"103362","DOI":"10.1016\/j.arcmed.2025.103362","article-title":"Cardiomyopathy in Northwestern Mexico: Clinical Spectrum, Morphological Variants, and Sarcomere Gene Mutations","volume":"57","year":"2026","journal-title":"Arch. Med. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1161\/CIRCULATIONAHA.123.065987","article-title":"Meta-Analysis of Penetrance and Systematic Review on Transition to Disease in Genetic Hypertrophic Cardiomyopathy","volume":"149","author":"Topriceanu","year":"2024","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Dababneh, S., Ardehali, A., Badesha, J., and Laksman, Z. (2025). The Utility of Genome-Wide Association Studies in Inherited Arrhythmias and Cardiomyopathies. Genes, 16.","DOI":"10.3390\/genes16121448"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1161\/CIRCULATIONAHA.124.073475","article-title":"Genotype-Specific Outcomes of Desmosomal Cardiomyopathies","volume":"152","author":"Pergola","year":"2025","journal-title":"Circulation"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jjcc.2018.09.005","article-title":"Novel phenotype-genotype correlations of hypertrophic cardiomyopathy caused by mutation in \u03b1-actin and myosin-binding protein genes in three unrelated Chinese families","volume":"73","author":"Yang","year":"2019","journal-title":"J. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Thanassoulas, A., Riguene, E., Theodoridou, M., Barrak, L., Almaraghi, H., Hussain, M., Da\u2019as, S.I., Elrayess, M.A., Lai, F.A., and Nomikos, M. (2025). Disparate Molecular Properties of Two Hypertrophic Cardiomyopathy-Associated cMyBP-C Mutants Reveal Distinct Pathogenic Mechanisms Beyond Haploinsufficiency. Biomedicines, 13.","DOI":"10.3390\/biomedicines13051010"},{"key":"ref_50","first-page":"e99069","article-title":"The Genetic Landscape of Familial Hypercholesterolemia in Telangana, Southern India: Novel Mutations and Clinical Implications","volume":"17","author":"Garapati","year":"2025","journal-title":"Cureus"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1016\/j.jacc.2010.02.015","article-title":"2010 ACCF\/AHA\/AATS\/ACR\/ASA\/SCA\/SCAI\/SIR\/STS\/SVM Guidelines for the Diagnosis and Management of Patients with Thoracic Aortic Disease","volume":"55","author":"Hiratzka","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Authors\/Task Force Members, Czerny, M., Grabenw\u00f6ger, M., Berger, T., Aboyans, V., Della Corte, A., Chen, E.P., Desai, N.D., Dumfarth, J., and Elefteriades, J.A. (2024). EACTS\/STS Guidelines for Diagnosing and Treating Acute and Chronic Syndromes of the Aortic Organ. Ann. Thorac. Surg., 118, 5\u2013115.","DOI":"10.1016\/j.athoracsur.2024.01.021"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1007\/s00247-003-1116-1","article-title":"Age-related normal ranges for the Haller index in children","volume":"34","author":"Daunt","year":"2004","journal-title":"Pediatr. Radiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/humu.20654","article-title":"Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker","volume":"29","author":"Wildeman","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1093\/hmg\/ddg241","article-title":"Allelic variation in normal human FBN1 expression in a family with Marfan syndrome: A potential modifier of phenotype?","volume":"12","author":"Hutchinson","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1542\/peds.27.2.255","article-title":"Early manifestations of the cardiovascular disorders in Marfan syndrome","volume":"27","author":"Papaioannou","year":"1961","journal-title":"Pediatrics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1097\/00000658-197112000-00004","article-title":"Aneurysms of all sinuses of Valsalva in patients with Marfan\u2019s syndrome: An unusual late complication following replacement of aortic valve and ascending aorta for aortic regurgitation and fusiform aneurysm of ascending aorta","volume":"174","author":"Symbas","year":"1971","journal-title":"Ann. Surg."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Toutounji, K., Safi, D., El Rassi, I., and Arabi, M. (2025). Beyond the Heart: Marfan Syndrome from the Cardiologist\u2019s Perspective. Cardiol. Rev., Online ahead of print.","DOI":"10.1097\/CRD.0000000000001131"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1002\/ajmg.a.36463","article-title":"Exome analysis of connective tissue dysplasia: Death and rebirth of clinical genetics?","volume":"164","author":"Wilson","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/ajmg.a.38004","article-title":"Ehlers-Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in FLNA","volume":"173","author":"Ritelli","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/(SICI)1098-1004(1997)10:6<415::AID-HUMU1>3.0.CO;2-C","article-title":"Fibrillin-1 mutations in Marfan syndrome and other type-1 fibrillinopathies","volume":"10","author":"Hayward","year":"1997","journal-title":"Hum. Mutat."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"27172","DOI":"10.1038\/s41598-024-78788-3","article-title":"Genetic insights from a Brazilian cohort of aortopathies through targeted next-generation sequencing and FBN1 direct sequencing","volume":"14","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ng1116","article-title":"Dysregulation of TGF-\u03b2 activation contributes to pathogenesis in Marfan syndrome","volume":"33","author":"Neptune","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1172\/JCI200420641","article-title":"Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome","volume":"114","author":"Judge","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1083\/jcb.200608167","article-title":"Fibrillin-1 regulates the bioavailability of TGF\u03b21","volume":"176","author":"Chaudhry","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/S0929-6646(10)60110-6","article-title":"Fatal Tuberculous Myositis in an Immunocompromised Adult with Primary Sj\u00f6gren\u2019s Syndrome","volume":"109","author":"Huang","year":"2010","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1086\/521409","article-title":"Marfan syndrome: From molecules to medicines","volume":"81","author":"Dietz","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1085\/jgp.201812238","article-title":"Recovery of left ventricular function following in vivo reexpression of cardiac myosin binding protein C","volume":"151","author":"Giles","year":"2019","journal-title":"J. Gen. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.matbio.2024.01.003","article-title":"Three-dimensional co-culturing of stem cell-derived cardiomyocytes and cardiac fibroblasts reveals a role for both cell types in Marfan-related cardiomyopathy","volume":"126","author":"Aalders","year":"2024","journal-title":"Matrix Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.cellbio.12.1.463","article-title":"Focal adhesions, contractility, and signaling","volume":"12","author":"Burridge","year":"1996","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/0955-0674(91)90060-C","article-title":"Transmembrane molecular assemblies regulated by the greater cadherin family","volume":"3","author":"Magee","year":"1991","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1083\/jcb.126.1.111","article-title":"Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: Implications for human disease","volume":"126","author":"Lisanti","year":"1994","journal-title":"J. Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3109\/09687689509038506","article-title":"Caveolae, transmembrane signalling and cellular transformation","volume":"12","author":"Lisanti","year":"1995","journal-title":"Mol. Membr. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1126\/science.276.5317.1425","article-title":"Geometric control of cell life and death","volume":"276","author":"Chen","year":"1997","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0955-0674(97)80159-7","article-title":"mRNA and cytoskeletal filaments","volume":"9","author":"Bassell","year":"1997","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/1357-2725(96)00059-3","article-title":"The compartmentalization of protein synthesis: Importance of cytoskeleton and role in mRNA targeting","volume":"28","author":"Hovland","year":"1996","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0955-0674(97)80158-5","article-title":"Cytoskeletal and adhesion proteins as tumor suppressors","volume":"9","year":"1997","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0955-0674(97)80151-2","article-title":"Intermediate filaments and cytoplasmic networking: New connections and more functions","volume":"9","author":"Chou","year":"1997","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.matbio.2018.01.013","article-title":"Extracellular matrix remodeling and cardiac fibrosis","volume":"68\u201369","author":"Li","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Rozen, T.D., Bruno, K.A., Rozen, E.M., Wilson, F.C., Tweet, M.S., Shields, R.C., Hayes, S.N., Knight, D.R.T., Gajarawala, S.N., and Sandhu, S.J.S. (2026). Prevalence of Intracranial and Cervical Artery Abnormalities in Patients with Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders Presenting to an Academic Headache Clinic. Neurol. Int., 18.","DOI":"10.3390\/neurolint18020033"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.3171\/2022.9.JNS221373","article-title":"Relationship between phenotypic features in Loeys-Dietz syndrome and the presence of intracranial aneurysms","volume":"138","author":"Huguenard","year":"2023","journal-title":"J. Neurosurg."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"102731","DOI":"10.1016\/j.jaccas.2024.102731","article-title":"Comprehensive Genetic Testing for Coexisting Marfan and Loeys-Dietz Syndromes in Hereditary Thoracic Aortic Disease","volume":"29","author":"Yoshida","year":"2024","journal-title":"JACC Case Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"071001","DOI":"10.1115\/1.4024349","article-title":"The role of cardiac fibroblasts in extracellular matrix-mediated signaling during normal and pathological cardiac development","volume":"135","author":"Sullivan","year":"2013","journal-title":"J. Biomech. Eng."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Kim, K.K., Sheppard, D., and Chapman, H.A. (2018). TGF-\u03b21 Signaling and Tissue Fibrosis. Cold Spring Harb. Perspect. Biol., 10.","DOI":"10.1101\/cshperspect.a022293"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0022-2828(85)90005-7","article-title":"Calcium and catecholamines: Relevance to cardiomyopathies and significance in therapeutic strategies","volume":"17","author":"Opie","year":"1985","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1016\/j.jacc.2014.01.041","article-title":"Incidence and causes of sudden death in U.S. college athletes","volume":"63","author":"Maron","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1016\/j.jacc.2003.03.002","article-title":"Does sports activity enhance the risk of sudden death in adolescents and young adults?","volume":"42","author":"Corrado","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1161\/CIRCULATIONAHA.108.804617","article-title":"Sudden deaths in young competitive athletes: Analysis of 1866 deaths in the United States, 1980\u20132006","volume":"119","author":"Maron","year":"2009","journal-title":"Circulation"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1001\/jama.296.13.1593","article-title":"Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program","volume":"296","author":"Corrado","year":"2006","journal-title":"JAMA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1536\/ihj.26.1043","article-title":"Myocardial involvement in the Marfan syndrome","volume":"26","author":"Fujiseki","year":"1985","journal-title":"Jpn. Heart J."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Xie, X., He, Y., Chen, Y., Li, Z., Sun, Y., and Chen, G. (2026). Functional Characterization of the SCN5A p.D372H Variant Associated with Brugada Syndrome. Biomedicines, 14.","DOI":"10.3390\/biomedicines14030582"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s11011-021-00671-1","article-title":"A novel de novo heterozygous pathogenic variant in the SDHA gene results in childhood onset bilateral optic atrophy and cognitive impairment","volume":"36","author":"Zehavi","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1161\/CIRCRESAHA.122.321956","article-title":"Slower Calcium Handling Balances Faster Cross-Bridge Cycling in Human MYBPC3 HCM","volume":"132","author":"Pioner","year":"2023","journal-title":"Circ. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s12276-023-00953-x","article-title":"Etiology of genetic muscle disorders induced by mutations in fast and slow skeletal MyBP-C paralogs","volume":"55","author":"Song","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1086\/520125","article-title":"Effect of mutation type and location on clinical outcome in 1013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: An international study","volume":"81","author":"Faivre","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"582","DOI":"10.21037\/acs.2017.11.03","article-title":"Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome","volume":"6","author":"Meester","year":"2017","journal-title":"Ann. Cardiothorac. Surg."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/11\/1001\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:21:38Z","timestamp":1780633298000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/11\/1001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":97,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["cells15111001"],"URL":"https:\/\/doi.org\/10.3390\/cells15111001","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]}}}