Exome Sequencing Identifies Genetic Variants Associated with Extreme Manifestations of the Cardiovascular Phenotype in Marfan Syndrome

Journal
Genes
ISSN
2073-4425
Date Issued
2022
Author(s)
Yanireth Jimenez
Cesar Paulsen
Eduardo Turner
Sebastian Iturra
Oscar Cuevas
Guillermo Lay-son
Marcelo Rojas
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85132687729
WoS ID
WOS:000815892800001
DOI
URL
URL Institutional Repository
Abstract
<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>
Cite this document
Jimenez, 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/genes13061027
Project(s)
Dataset(s)
Subjects
smooth-muscle-cells

; 

extracellular-matrix

; 

aortic dissection

; 

activation

; 

receptor

; 

fbn1

; 

disruption

; 

apoptosis

; 

jcad/kiaa1462

; 

pathogenesis

; 

exome

; 

fibrillin-1

; 

humans

; 

marfan syndrome

; 

mutation

; 

phenotype

; 

cyclin d1

; 

cyclin d3

; 

elastase

; 

elastin

; 

fibrillin 1

; 

fibronectin

; 

gelatinase a

; 

gelatinase b

; 

low density lipoprotein

; 

mitogen activated protein kinase kinase kinase 1

; 

notch1 receptor

; 

notch4 receptor

; 

peroxisome proliferator activated receptor delta

; 

protein jagged 1

; 

stat1 protein

; 

transforming growth factor beta

; 

vascular cell adhesion molecule 1

; 

vasculotropin

; 

vasculotropin receptor 2

; 

fibrillin 1

; 

angiogenesis

; 

aortic aneurysm

; 

apoptosis

; 

article

; 

cardiovascular disease

; 

chronic obstructive lung disease

; 

computer model

; 

coronary artery disease

; 

disease severity

; 

dissecting aortic aneurysm

; 

ectopia lentis

; 

extracellular matrix

; 

gene mutation

; 

gene ontology

; 

genetic conservation

; 

genetic variability

; 

human

; 

marfan syndrome

; 

mortality

; 

pathophysiology

; 

phenotype

; 

signal transduction

; 

whole exome sequencing

; 

exome

; 

genetics

; 

mutation

; 

phenotype