Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting

The Annals of Thoracic Surgery

Available online 15 July 2015

In Press, Corrected Proof — Note to users

Original article

Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting

Presented at the Poster Session of the Fifty-first Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 24–28, 2015.

• Bulat A. Ziganshin, MD^a, 
• Allison E. Bailey, BS^b, 
• Celinez Coons^b, 
• Daniel Dykas, BS^b,
• Paris Charilaou, MD^a, 
• Lokman H. Tanriverdi^a, 
• Lucy Liu, BS^a, 
• Maryann Tranquilli, RN^a,
• Allen E. Bale, MD^b, 
• John A. Elefteriades, MD^a, , 

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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). Here we present our initial results.

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.

Address correspondence to Dr Elefteriades, 789 Howard Ave, Clinic Bldg CB317, New Haven, CT 06519.

Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

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