{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:06:33Z","timestamp":1791389193842,"version":"4.3.3"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Congenital heart diseases (CHDs) are the most common inherited anomalies worldwide and remain a major cause of mortality in pediatric populations. Advances in genomic medicine have improved the ability to identify molecular mechanisms underlying complex CHD phenotypes, including cases not fully explained by a single-gene disorder.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      This case presents an Ecuadorian girl with the coexistence of congenital supravalvar aortic stenosis and congenital valvar pulmonary stenosis. Molecular analysis identified pathogenic variants in\n                      <jats:italic>ELN<\/jats:italic>\n                      and\n                      <jats:italic>BRAF<\/jats:italic>\n                      , together with a\n                      <jats:italic>NOTCH1<\/jats:italic>\n                      p.(Leu2429Arg) variant of uncertain significance (VUS). Ancestry analysis revealed an admixed background with predominant European ancestry, followed by Native American and African components.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Findings are consistent with a multilocus in which ELN and BRAF variants may biologically plausibly contribute to the observed phenotype; however, this should be taken cautiously as more evidence, and studies must be performed to understand the impact of these variants. This case also highlights the importance of generating cardiogenetic evidence from underrepresented Latin American populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Comprehensive genomic evaluation can refine etiologic diagnosis, reveal blended mechanisms in CHD, and support precision medicine approaches. This report contributes to the growing role of advanced genetic testing in the future management of CHD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1868988","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:20:54Z","timestamp":1783923654000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Dual molecular diagnosis in complex congenital heart disease in an Ecuadorian patient with supravalvar aortic stenosis and pulmonary valve stenosis carrying pathogenic variants in ELN and BRAF gene"],"prefix":"10.3389","volume":"14","author":[{"given":"Santiago","family":"Cadena-Ullauri","sequence":"first","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana A.","family":"Ruiz-Pozo","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Tamayo-Trujillo","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Guevara-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elius","family":"Paz-Cruz","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Bossano R","sequence":"additional","affiliation":[{"name":"Private Practice Pediatric Cardiologist","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Hinojosa","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Onofre-Ruiz","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Karina","family":"Zambrano","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n Gen\u00e9tica y Gen\u00f3mica","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/s41569-022-00749-y","article-title":"Changing epidemiology of congenital heart disease: effect on outcomes and quality of care in adults","volume":"20","author":"Liu","year":"2023","journal-title":"Nat Rev Cardiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/S2352-4642(23)00076-7","article-title":"Current treatment outcomes of congenital heart disease and future perspectives","volume":"7","author":"Ma","year":"2023","journal-title":"Lancet Child Adolesc Health"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1522644","DOI":"10.3389\/FCVM.2025.1522644\/FULL","article-title":"Global, regional, and national epidemiology of congenital heart disease in children from 1990 to 2021","volume":"12","author":"Xu","year":"2025","journal-title":"Front Cardiovasc Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e010657","DOI":"10.1161\/CIRCOUTCOMES.123.010657","article-title":"Population-based estimates of the prevalence of children with congenital heart disease and associated comorbidities in the United States","volume":"17","author":"Parker","year":"2024","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"B5","doi-asserted-by":"publisher","first-page":"11","DOI":"10.5334\/gh.1288","article-title":"The heart of the world","volume":"19","author":"Di Cesare","year":"2024","journal-title":"Glob Heart"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1016\/J.JACC.2025.08.015","article-title":"Global, regional, and national burden of cardiovascular diseases and risk factors in 204 countries and territories, 1990\u20132023","volume":"86","author":"Stark","year":"2025","journal-title":"J Am Coll Cardiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"11896","DOI":"10.3390\/IJMS262411896","article-title":"Spectrum and clinical interpretation of TTN variants in Ecuadorian patients with heart disease: insights into VUS and likely pathogenic variants","volume":"26","author":"Guevara-Ram\u00edrez","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"186","DOI":"10.14740\/jmc.v15i8.4250","article-title":"Exploring atrial fibrillation: understanding the complex relation between lifestyle and genetic factors","volume":"15","author":"Tamayo-Trujillo","year":"2024","journal-title":"J Med Cases"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1552423","DOI":"10.3389\/FCVM.2025.1552423\/TEXT","article-title":"Identification of a novel NKX2-5 variant in a young Ecuadorian patient with atrioventricular block and bradycardia: a case report","volume":"12","author":"Ruiz-Pozo","year":"2025","journal-title":"Front Cardiovasc Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.1037370","article-title":"Case report: genomic screening for inherited cardiac conditions in Ecuadorian mestizo relatives: improving familial diagnose","volume":"9","author":"Cadena-Ullauri","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e631","DOI":"10.1002\/MCO2.631","article-title":"Congenital heart disease: types, pathophysiology, diagnosis, and treatment options","volume":"5","author":"Meng","year":"2024","journal-title":"MedComm (Beijing)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1017\/S1047951117002244","article-title":"Nomenclature for congenital and paediatric cardiac disease: the international paediatric and congenital cardiac code (IPCCC) and the eleventh iteration of the international classification of diseases (ICD-11)","volume":"27","author":"Franklin","year":"2017","journal-title":"Cardiol Young"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e003355","DOI":"10.1136\/OPENHRT-2025-003355","article-title":"Clinical course and outcomes of supravalvular aortic stenosis in adults","volume":"12","author":"De Keijzer","year":"2025","journal-title":"Open Heart"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/EJCTS\/EZAD429","article-title":"Supravalvular aortic stenosis: the long-term story of a mischievous disease","volume":"65","author":"Guariento","year":"2024","journal-title":"Eur J Cardiothorac Surg"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e034048","DOI":"10.1161\/JAHA.123.034048","article-title":"Genetic testing for supravalvar aortic stenosis: what to do when it is not williams syndrome","volume":"13","author":"Stephens","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1059640","DOI":"10.3389\/fgene.2022.1059640","article-title":"Identification and characterization of novel elastin gene mutations in eleven families with supravalvular aortic stenosis","volume":"13","author":"Zhou","year":"2022","journal-title":"Front Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1161\/CIRCGENETICS.112.962860","article-title":"Supravalvular aortic stenosis","volume":"26","author":"Merla","year":"2012","journal-title":"Circ: Cardiovasc Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/J.CARREV.2025.04.027","article-title":"Supravalvular aortic stenosis\u2014novel pathogenic ELN variant in siblings with a wide spectrum of clinical cardiovascular features and a long follow-up from infancy to adulthood","volume":"83","author":"Keskinen","year":"2026","journal-title":"Cardiovasc Revasc Med"},{"key":"B19","first-page":"803","volume-title":"Pulmonary Stenosis","author":"Heaton","year":"2024"},{"key":"B20","doi-asserted-by":"publisher","first-page":"379","DOI":"10.2147\/VHRM.S380240","article-title":"Pulmonary valve stenosis: from diagnosis to current management techniques and future prospects","volume":"19","author":"Marchini","year":"2023","journal-title":"Vasc Health Risk Manag"},{"key":"B21","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/B978-0-12-420219-1.00014-8","article-title":"Congenital heart disease: pathology, natural history, and interventions","volume":"4","author":"Ottaviani","year":"2016","journal-title":"Cardiovasc Pathol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1002\/AJMG.C.32014","article-title":"The heart in RASopathies","volume":"190","author":"Delogu","year":"2022","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1176828","DOI":"10.3389\/FCVM.2023.1176828","article-title":"RASopathies and cardiac manifestations","volume":"10","author":"Hilal","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.3390\/GENES15081015","article-title":"Cardiac phenotype and gene mutations in RASopathies","volume":"15","author":"Faienza","year":"2024","journal-title":"Genes (Basel)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"915129","DOI":"10.3389\/FGENE.2022.915129\/TEXT","article-title":"Cardiovascular abnormalities and gene mutations in children with noonan syndrome","volume":"13","author":"Sun","year":"2022","journal-title":"Front Genet"},{"key":"B26","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/S40659-021-00342-6","article-title":"Molecules linked to ras signaling as therapeutic targets in cardiac pathologies","volume":"54","author":"Ramos-Kuri","year":"2021","journal-title":"Biol Res"},{"key":"B27","volume-title":"Congenital Heart Defects\u2014diagnosis","year":"2022"},{"key":"B28","doi-asserted-by":"publisher","first-page":"12677","DOI":"10.1038\/s41598-026-42761-z","article-title":"Noninvasive hemodynamic assessment of aortic coarctation: multimodal imaging based-computational fluid dynamics","volume":"16","author":"Hu","year":"2026","journal-title":"Sci Rep"},{"key":"B29","volume-title":"Congenital Heart Defects (CHD)","year":"2026"},{"key":"B30","doi-asserted-by":"publisher","first-page":"79","DOI":"10.21037\/QIMS.2017.02.04","article-title":"Computed tomography in congenital heart disease: how generic principles can be applied to create bespoke protocols in the Fontan circuit","volume":"7","author":"Loughborough","year":"2017","journal-title":"Quant Imaging Med Surg"},{"key":"B31","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1097\/MOP.0000000000000538","article-title":"The genetics of congenital heart disease\u2026understanding and improving long term outcomes in congenital heart disease: a review for the general cardiologist and primary care physician","volume":"29","author":"Abigail Simmons","year":"2017","journal-title":"Curr Opin Pediatr"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/JPC.70176","article-title":"The evolving landscape of CHD genetics: a contemporary guide to genetic testing and management","author":"O\u2019Malley","year":"2025","journal-title":"J Paediatr Child Health"},{"key":"B33","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1517\/21678707.2015.1057498.Diagnosis","article-title":"Diagnosis, prevalence, and screening of familial dilated cardiomyopathy","volume":"3","author":"Sweet","year":"2016","journal-title":"Expert Opin Orphan Drugs"},{"key":"B34","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1161\/CIRCULATIONAHA.116.024258","article-title":"Next-generation sequencing in cardiovascular disease: present clinical applications and the horizon of precision medicine","volume":"135","author":"Parikh","year":"2017","journal-title":"Circulation"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2544","DOI":"10.3390\/JCM13092544","article-title":"Clinical genetic and genomic testing in congenital heart disease and cardiomyopathy","volume":"13","author":"Pidaparti","year":"2024","journal-title":"J Clin Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"27312","DOI":"10.1038\/s41598-025-06977-9","article-title":"Genetic findings of children with congenital heart diseases using chromosomal microarray and trio-based whole exome sequencing","volume":"15","author":"Guo","year":"2025","journal-title":"Sci Rep"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.125.005367","article-title":"Rapid genome sequencing shows diagnostic utility in infants with congenital heart defects","volume":"19","author":"Durbin","year":"2026","journal-title":"Circ Genom Precis Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1395012","article-title":"Identifying genomic variant associated with long QT syndrome type 2 in an Ecuadorian mestizo individual: a case report","volume":"15","author":"Tamayo-Trujillo","year":"2024","journal-title":"Front Genet"},{"key":"B39","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1055\/S-0044-1779469","article-title":"Exploring health care disparities in genetic testing and research for hereditary cardiomyopathy: current state and future perspectives","volume":"11","author":"Huang","year":"2024","journal-title":"Glob Med Genet"},{"key":"B40","first-page":"688","article-title":"Genealogy of patients with congenital heart disease in isolated populations","volume":"11","author":"Mart\u00ednez-Quintana","year":"2021","journal-title":"Am J Cardiovasc Dis"},{"key":"B41","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1161\/CIRCGEN.124.005039","article-title":"Genetic variants associated with congenital heart disease: a meta-analysis of ethnicity and subtype-specific susceptibility","volume":"18","author":"Chon","year":"2025","journal-title":"Circ Genom Precis Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1680300","DOI":"10.3389\/FCVM.2026.1680300\/TEXT","article-title":"Case report series: genetic and clinical characterization of long QT syndrome in admixed Ecuadorian patients and its implications for sudden cardiac death risk","volume":"13","author":"Paz-Cruz","year":"2026","journal-title":"Front Cardiovasc Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1693244","DOI":"10.3389\/FCVM.2025.1693244\/TEXT","article-title":"Case report: genomic and clinical insights into MYBPC3-related hypertrophic cardiomyopathy in Ecuadorian patients: implications for sudden cardiac death risk","volume":"12","author":"Paz-Cruz","year":"2026","journal-title":"Front Cardiovasc Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-024-04049-w","article-title":"Genomic analysis of an Ecuadorian individual carrying an SCN5A rare variant","volume":"24","author":"Cadena-Ullauri","year":"2024","journal-title":"BMC Cardiovasc Disord"},{"key":"B45","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41569-021-00587-4","article-title":"Genomic frontiers in congenital heart disease","volume":"19","author":"Morton","year":"2021","journal-title":"Nat Rev Cardiol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/S11936-025-01091-5","article-title":"Genetic and environmental contributors to congenital heart disease","volume":"27","author":"Choudhury","year":"2025","journal-title":"Curr Treat Options Cardiovasc Med"},{"key":"B47","doi-asserted-by":"publisher","first-page":"a013953","DOI":"10.1101\/CSHPERSPECT.A013953","article-title":"Complex genetics and the etiology of human congenital heart disease","volume":"4","author":"Gelb","year":"2014","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1038\/NG.3970","article-title":"Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands","volume":"49","author":"Jin","year":"2017","journal-title":"Nat Genet"},{"key":"B49","doi-asserted-by":"publisher","first-page":"a037234","DOI":"10.1101\/CSHPERSPECT.A037234","article-title":"Environmental risk factors for congenital heart disease","volume":"12","author":"Kalisch-Smith","year":"2020","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1126\/SCIENCE.AAT5056","article-title":"Oligogenic inheritance of a human heart disease involving a genetic modifier","volume":"364","author":"Gifford","year":"2019","journal-title":"Science"},{"key":"B51","doi-asserted-by":"publisher","first-page":"101673","DOI":"10.1016\/J.JACADV.2025.101673","article-title":"Polygenic inheritance for common comorbidities associated with congenital heart disease","volume":"4","author":"Thompson","year":"2025","journal-title":"JACC Adv"},{"key":"B52","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/jhg.2015.98","article-title":"Genetics of congenital heart disease: the contribution of the noncoding regulatory genome","volume":"61","author":"Postma A","year":"2016","journal-title":"J Hum Genet"},{"key":"B53","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/J.BJ.2021.06.004","article-title":"RASopathies: from germline mutations to somatic and multigenic diseases","volume":"44","author":"Riller","year":"2021","journal-title":"Biomed J"},{"key":"B54","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1007\/S00246-022-03089-3","article-title":"Sudden cardiac arrest during a sedated cardiac magnetic resonance study in a nonsyndromic child with evolving supravalvar aortic stenosis due to familial ELN mutation","volume":"44","author":"Markush","year":"2023","journal-title":"Pediatr Cardiol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1186\/S12887-023-04408-0","article-title":"Novel mutation in ELN gene causes cardiac abnormalities and inguinal hernia: case report","volume":"23","author":"Zhang","year":"2023","journal-title":"BMC Pediatr"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1007\/S00246-024-03418-8","article-title":"Fetal diagnosis of supravalvular aortic stenosis and pulmonary stenosis in a family with non-syndromic elastin mutation","volume":"45","author":"Kiener","year":"2024","journal-title":"Pediatr Cardiol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1671066","DOI":"10.3389\/FPED.2026.1671066\/FULL","article-title":"Case report: newly discovered ELN gene mutation in congenital heart disease: case analysis and review","volume":"14","author":"Cheng","year":"2026","journal-title":"Front Pediatr"},{"key":"B58","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-981-16-5812-9_2","article-title":"The GeneCards suite","volume-title":"Practical Guide to Life Science Databases","author":"Safran","year":"2021"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1.30.1","DOI":"10.1002\/cpbi.5","article-title":"The GeneCards suite: from gene data mining to disease genome sequence analyses","volume":"2016","author":"Stelzer","year":"2016","journal-title":"Curr Protoc Bioinform"},{"key":"B60","volume-title":"Franklin by Genoox v86.3","year":"2014"},{"key":"B61","doi-asserted-by":"publisher","first-page":"D980","DOI":"10.1093\/NAR\/GKT1113","article-title":"Clinvar: public archive of relationships among sequence variation and human phenotype","volume":"42","author":"Landrum","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"B62","doi-asserted-by":"publisher","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":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-025-63340-2","article-title":"Improved allele frequencies in gnomAD through local ancestry inference","volume":"16","author":"Kore","year":"2025","journal-title":"Nat Commun"},{"key":"B64","doi-asserted-by":"publisher","first-page":"113351","DOI":"10.1016\/J.JPEDS.2022.12.045","article-title":"Cardiovascular characteristics and progressions of hypertrophic cardiomyopathy and pulmonary stenosis in RASopathy syndrome in the genomic era","volume":"262","author":"Kim","year":"2023","journal-title":"J Pediatr"},{"key":"B65","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3390\/BIOCHEM5040038","article-title":"RASopathy and sudden cardiac death: a literature review","volume":"5","author":"Salzillo","year":"2025","journal-title":"BioChem"},{"key":"B66","doi-asserted-by":"publisher","first-page":"4262","DOI":"10.1016\/J.MOLCEL.2022.10.016","article-title":"RASopathy mutations provide functional insight into the BRAF cysteine-rich domain and reveal the importance of autoinhibition in BRAF regulation","volume":"82","author":"Spencer-Smith","year":"2022","journal-title":"Mol Cell"},{"key":"B67","doi-asserted-by":"publisher","first-page":"4262","DOI":"10.7759\/cureus.92607","article-title":"Coexistence of severe valvular pulmonary stenosis and papillary thyroid carcinoma: a rare association or coincidence?","volume":"22","author":"Alshehri","year":"2025","journal-title":"Cureus"},{"key":"B68","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1038\/S41431-024-01629-4","article-title":"Expanding the phenotypic spectrum of NOTCH1 variants: clinical manifestations in families with congenital heart disease","volume":"32","author":"Stanley","year":"2024","journal-title":"Eur J Hum Genet"},{"key":"B69","doi-asserted-by":"publisher","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.Org: online Mendelian Inheritance in Man (OMIM\u00ae), an online catalog of human genes and genetic disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B70","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/S41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"B71","doi-asserted-by":"publisher","first-page":"a017145","DOI":"10.1101\/CSHPERSPECT.A017145","article-title":"Genetic modifiers and oligogenic inheritance","volume":"5","author":"Kousi","year":"2015","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B72","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3390\/GENES11030239","article-title":"Genetic modifiers and rare Mendelian disease","volume":"11","author":"Rahit","year":"2020","journal-title":"Genes (Basel)"},{"key":"B73","doi-asserted-by":"publisher","first-page":"409","DOI":"10.14740\/cr1552","article-title":"Associations of MYPN, TTN, SCN5A, MYO6 and ELN mutations with arrhythmias and subsequent sudden cardiac death: a case report of an Ecuadorian individual","volume":"14","author":"Paz-Cruz","year":"2023","journal-title":"Cardiol Res"},{"key":"B74","doi-asserted-by":"publisher","first-page":"e59497","DOI":"10.7759\/CUREUS.59497","article-title":"Racial and socioeconomic determinants of cardiovascular health: a comprehensive review","volume":"16","author":"Borkowski","year":"2024","journal-title":"Cureus"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.5888\/PCD22.240270","article-title":"Disparities in cardiovascular disease prevalence by race and ethnicity, socioeconomic status, urbanicity, and social determinants of health among medicare beneficiaries with diabetes","volume":"22","author":"Zhou","year":"2025","journal-title":"Prev Chronic Dis"},{"key":"B76","doi-asserted-by":"publisher","first-page":"E007917","DOI":"10.1161\/CIRCOUTCOMES.121.007917","article-title":"Race, racism, and cardiovascular health: applying a social determinants of health framework to racial\/ethnic disparities in cardiovascular disease","volume":"15","author":"Javed","year":"2022","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"B77","doi-asserted-by":"publisher","first-page":"e3050","DOI":"10.5867\/MEDWAVE.2025.06.3050","article-title":"Characterization of a variant in the KCNH2 gene in an Ecuadorian patient with long QT syndrome: a case report","volume":"25","author":"Cadena-Ullauri","year":"2025","journal-title":"Medwave"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1141083","article-title":"Genomic analysis of a novel pathogenic variant in the gene LMNA associated with cardiac laminopathies found in Ecuadorian siblings: a case report","volume":"10","author":"Guevara-Ram\u00edrez","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45723-w","article-title":"The three-hybrid genetic composition of an Ecuadorian population using AIMs-InDels compared with autosomes, mitochondrial DNA and Y chromosome data","volume":"9","author":"Zambrano","year":"2019","journal-title":"Sci Rep"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1868988\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:20:56Z","timestamp":1783923656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1868988\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":79,"alternative-id":["10.3389\/fped.2026.1868988"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1868988","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]},"article-number":"1868988"}}