Yanireth JimenezCesar PaulsenEduardo TurnerSebastian IturraOscar CuevasGuillermo Lay-sonREPETTO LISBOA, MARIA GABRIELAMARIA GABRIELAREPETTO LISBOAMarcelo RojasCALDERON GIADROSIC, JUAN FRANCISCOJUAN FRANCISCOCALDERON GIADROSIC2023-01-252023-01-252022Jimenez, Y., Paulsen, C., Turner, E., Iturra, S., Cuevas, O., Lay-son, G., Repetto, G. M., Rojas, M., & Calderon, J. F. (2022). Exome sequencing identifies genetic variants associated with extreme manifestations of the cardiovascular phenotype in marfan syndrome. Genes, 13(6), 1027. https://doi.org/10.3390/genes13061027http://hdl.handle.net/11447/6763https://investigadores.udd.cl/handle/123456789/549510.3390/genes130610272-s2.0-85132687729WOS:000815892800001<jats:p>Marfan Syndrome (MFS) is an autosomal dominant condition caused by variants in the fibrillin-1 (FBN1) gene. Cardinal features of MFS include ectopia lentis (EL), musculoskeletal features and aortic root aneurysm and dissection. Although dissection of the ascending aorta is the main cause of mortality in MFS, the clinical course differs considerably in age of onset and severity, even among individuals who share the same causative variant, suggesting the existence of additional genetic variants that modify the severity of the cardiovascular phenotype in MFS. We recruited MFS patients and classified them into severe (n = 8) or mild aortic phenotype (n = 14) according to age of presentation of the first aorta-related incident. We used Exome Sequencing to identify the genetic variants associated with the severity of aortic manifestations and we performed linkage analysis where suitable. We found five genes associated with severe aortic phenotype and three genes that could be protective for this phenotype in MFS. These genes regulate components of the extracellular matrix, TGFβ pathway and other signaling pathways that are involved in the maintenance of the ECM or angiogenesis. Further studies will be required to understand the functional effect of these variants and explore novel, personalized risk management and, potentially, therapies for these patients.</jats:p>smooth-muscle-cellsextracellular-matrixaortic dissectionactivationreceptorfbn1disruptionapoptosisjcad/kiaa1462pathogenesisexomefibrillin-1humansmarfan syndromemutationphenotypecyclin d1cyclin d3elastaseelastinfibrillin 1fibronectingelatinase agelatinase blow density lipoproteinmitogen activated protein kinase kinase kinase 1notch1 receptornotch4 receptorperoxisome proliferator activated receptor deltaprotein jagged 1stat1 proteintransforming growth factor betavascular cell adhesion molecule 1vasculotropinvasculotropin receptor 2fibrillin 1angiogenesisaortic aneurysmapoptosisarticlecardiovascular diseasechronic obstructive lung diseasecomputer modelcoronary artery diseasedisease severitydissecting aortic aneurysmectopia lentisextracellular matrixgene mutationgene ontologygenetic conservationgenetic variabilityhumanmarfan syndromemortalitypathophysiologyphenotypesignal transductionwhole exome sequencingexomegeneticsmutationphenotypeResource Types::text::journal::journal article