Cardiology Online - International Academy of Cardiology
»search site
The International Academy of Cardiology is dedicated to the advancement of global research in cardiovascular medicine through the support of scientific meetings and publications.
   Home Page
   Discussion Groups
   Job Opportunities
   Contact Us





IAC 2018



John A. Elefteriades, M.D., Yale University School of Medicine, Aortic Institute at Yale-New Haven, New Haven, CT, USA


Background: Hereditary factors play an important etiologic role in thoracic aortic aneurysm and dissection (TAAD), with a number of genes proven to predispose to this condition. We initiated a clinical program for routine genetic testing of individuals for TAAD by whole exome sequencing (WES).
Methods: The WES was performed in 102 patients (mean age 56.8 years; range 13 to 83; 70 males [68.6%]) with TAAD. The following 21-gene panel was tested by WES: ACTA2, ADAMTS10, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ELN, FBLN4, FLNA, FBN1, FBN2, MYH11, MYLK, NOTCH1, PRKG1, SLC2A10, SMAD3, TGFB2, TGFBR1, TGFBR2. Results: Seventy-four patients (72.5%) had no medically important genetic alterations. Four patients (3.9%) had a deleterious mutation identified in the FBN1, COL5A1, MYLK, and FLNA genes. Twenty-two (21.6%) previously unreported suspicious variants of unknown significance were identified in 1 or more of the following genes: FBN1 (n [ 5); MYH11 (n [ 4); ACTA2 (n [ 2);COL1A1 (n [ 2); TGFBR1 (n [ 2); COL3A1 (n [ 1); COL5A1 (n [ 1); COL5A2 (n [ 1); FLNA (n [ 1); NOTCH1 (n [ 1); PRKG1 (n [ 1); and TGFBR3 (n [ 1).
Identified mutations had implications for clinical management.
Conclusions: Routine genetic screening of patients with TAAD provides information that enables genetically personalized care and permits identification of novel mutations responsible for aortic pathology. Analysis of large data sets of variants of unknown significance that include associated clinical features will help define the mutational spectrum of known genes underlying this phenotype and potential identify new candidate loci.



©1998-2020 Cardiology Online, Inc. All rights reserved.
Cardiology Online is a registered trademark of Cardiology Online, Inc.