Genetic Testing Can Detect, Protect Patients Prone To Thoracic Aortic Aneurysm

John A. Elefteriades, MD William W.L. Glenn Professor of Surgery Chief of Cardiothoracic Surgery Director, Aortic Institute at Yale-New Haven Yale University School of MedicineMedicalResearch.com Interview with:
John A. Elefteriades, MD
William W.L. Glenn Professor of Surgery
Chief of Cardiothoracic Surgery
Director, Aortic Institute at Yale-New Haven
Yale University School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Elefteriades: The race to map the human genome was declared completed in 2003, at a cost of 3 billion dollars for the international collaborative university group and 300 million dollars for Craig Venter at Celera. Whole exome sequencing can now be performed at a cost of only several thousand dollars per individual. So, whole exome sequencing (also called Next Generation Sequencing) can now be applied to understand and treat diseases of many organ systems.

In this study, we applied whole exome sequencing to study over 100 patients with thoracic aneurysm.

In the late 1990s, both Dr. Diana Milewicz in Texas and our group at Yale had determined that many thoracic aortic aneurysms were genetically transmitted. Dr. Milewicz went on to identify many of the causative mutations. In this study, we were able to look, by whole exome sequencing performed on saliva, for all 21 mutations known to cause thoracic aortic aneurysm–all at one time in one comprehensive genetic test. We were able to protect patients with the most serious discovered mutations by early surgery, the need for which could not otherwise have been apparent. 

Medical Research: What should clinicians and patients take away from your report?

Dr. Elefteriades: A comprehensive test for the genetic underpinnings of thoracic aortic aneurysm is now available. This is accomplished via whole exome sequencing (Next Generation Sequencing).

It can be extremely important for patients and their family members to have this testing done. Firstly, personalized care (including early surgery) can be performed for individuals with the most dangerous mutations (genetic alterations).

Secondly, if a mutation is indeed found, then a simple test on family members can determine which relatives will be vulnerable to thoracic aortic aneurysm and which are completely spared. The ones who are genetically spared can “forget” about the possibility of aneurysm disease, “like it never happened”.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Elefteriades: Widespread application of whole exome sequencing for thoracic aortic aneurysm will expand our roster of causative mutations rapidly and dramatically. We envision a “dictionary” or “encyclopedia” of mutations causing thoracic aneurysm that will number in the hundreds or thousands very soon.

Thoracic aortic aneurysm is a silent disease, lethal if not detected. Detection by genetic means will save vulnerable lives by permitting identification of disease and effective surgical therapy.

Citation:

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

Bulat A. Ziganshin, Allison E. Bailey, Celinez Coons, Daniel Dykas, Paris Charilaou, Lokman H. Tanriverdi, Lucy Liu, Maryann Tranquilli, Allen E. Bale, John A. Elefteriades

DOI: http://dx.doi.org/10.1016/j.athoracsur.2015.04.106
Publication stage: In Press Corrected Proof
Published online: July 15 2015

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John A. Elefteriades, MD (2015). Genetic Testing Can Detect, Protect Patients Prone To Thoracic Aortic Aneurysm