National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) and GenTAC Alliance

Project began
2006
Points of contact

What are the goals of the GenTAC Registry and GenTAC Alliance?

From 2006 to 2016, the NHLBI and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) co-funded the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). The purpose of the GenTAC Registry was to collect data and specimens from patients who had a confirmed or suspected genetic condition that increased their chances of developing thoracic aortic aneurysms. The data and specimens help physicians and researchers clarify the link between aortic disease and phenotypic and genotypic information.

By supporting the scientific community, the GenTAC Registry successfully promoted scientific collaborations and fostered research on thoracic aortic aneurysms. These collaborations resulted in publications that led to a greater understanding of the disease and improvements in patient health through better diagnosis and clinical care. Building on this success, in September 2017, the NHLBI began funding the GenTAC Alliance—a consortium of researchers, patients, professional and patient advocacy groups, and other stakeholders—that will coordinate the activities of the GenTAC Registry and other relevant registries.

The goals of the GenTAC Alliance include:

  • Enlarging partnerships to include other related registries, organizations, and industry partners with similar missions
  • Fostering new research collaborations that could lead to publications
  • Identifying new grants for research on thoracic aortic disease
  • Promoting education about genetically triggered thoracic aortic conditions
  • Translating state-of-the-art scientific discoveries into educational materials that generate effective conversations between health care providers and patients
  • Recruiting for clinical trials patients who have a genetic risk of developing thoracic aortic aneurysm and its complications, especially those affecting the heart and vascular systems
AT A GLANCE
  • The GenTAC Registry facilitated research in the diagnosis and clinical care of people who have genetically triggered thoracic aortic aneurysm.
  • The Registry enrolled over 3,600 people who had one of the 13 conditions with a genetic risk of developing thoracic aortic aneurysm and its complications.
  • The Registry has over 6,000 images, 2,000 blood samples, and 3,000 DNA samples, plus cardiovascular system and affected-organ data from over 3,600 patients.
  • The GenTAC Registry demonstrated the value of studying groups of participants with different genetic diseases who have similar cardiovascular outcomes.
  • After the GenTAC Registry ended, the GenTAC Alliance formed to expand collaborations and promote follow-up and enrollment in relevant registries.

How did the GenTAC Registry contribute to scientific discoveries?

The GenTAC Registry established a large biospecimen inventory and clinical database of over 3,600 participants that is available at no cost to qualified investigators worldwide. The Registry held biannual scientific meetings, monitored over 2,600 patients, contributed to findings in about 30 publications, and collected over 6,000 images, 2,000 blood samples, and 3,000 DNA samples, in addition to cardiovascular or affected-organ patient data.

The Registry also contributed to improving patient health through better diagnosis. Data have indicated that many thoracic aortic aneurysms in people younger than 50 are due to mutations in the genes. By providing clinical and biological data, the GenTAC Registry is helping improve the diagnosis and clinical care of genetically triggered thoracic aortic aneurysms and their complications, especially those affecting the cardiovascular system. View our YouTube playlist, which highlights genetics, imaging, and surgery options for thoracic aortic disease and research done using GenTAC data, biospecimens, or images.

Read more about how the GenTAC Registry continues to increase knowledge about thoracic aortic disease through Aortic Summits.

More Information

From 2009 to 2016, the GenTAC Registry held four scientific meetings called Aortic Summits, which help bring together clinical, translational, and basic scientists who research the genetic and other factors involved in the mechanisms of thoracic aortic disease, as well as its progression and treatment. Past Aortic Summits have included sessions on Turner, Ehlers-Danlos, Loeys-Dietz, and Marfan syndromes; familial and early-onset thoracic aortic aneurysms and dissections; and bicuspid aortic valve disease. They have also provided an opportunity to discuss current advances in the field. Learn more about the Aortic Summits in the News and Events section.

Patient data continue to be collected through the registries that resulted from the GenTAC Registry. The registries will continue to enroll participants and are available as a resource to researchers. These registries and contacts are:

  • Marfan Syndrome and Related Disorders
    Josephine Grima, Ph.D., Chief Scientific Officer, The Marfan Foundation

  • Vascular Ehlers–Danlos Syndrome
    Sherene Shalhub, M.D., M.P.H., University of Washington

  • Knight Cardiovascular Institute Aortic Disease Registry at Oregon Health & Science University
    Cheryl Maslen, Ph.D., Oregon Health & Science University
    Michael Silberbach, M.D., Oregon Health & Science University
    Derek Darby, Oregon Health & Science University

  • International Bicuspid Aortic Valve Consortium (BAVCon)
    Cheryl Maslen, Ph.D., Oregon Health & Science University
    Michael Silberbach, M.D., Oregon Health & Science University
    Simon Body, M.D., Harvard Medical School

  • Familial Thoracic Aortic Aneurysm Disease (FTAAD) Cohort and Montalcino Aortic Consortium (MAC)
    Dianna M. Milewicz, M.D., Ph.D., University of Texas at Houston
    Ellen Regalado, M.S., University of Texas at Houston
    Ellen Hostetler, University of Texas at Houston

  • Sporadic Aortic Dissection Cohort
    Dianna M. Milewicz, M.D., Ph.D., University of Texas at Houston
    Stephanie Wallace, M.S., University of Texas at Houston
    Ellen Hostetler, University of Texas at Houston

How can researchers access GenTAC Registry data?

The NHLBI’s Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) centralizes and integrates biospecimens and clinical data that are available to researchers online, which maximizes the value of these resources for many programs, including the GenTAC Registry. The NHLBI encourages researchers to utilize the valuable resources that have been collected in the Registry. Researchers may visit BioLINCC’s National Registry of GenTAC page to learn how to obtain GenTAC data, biospecimens, and images.

How was the GenTAC Registry conducted?

The GenTAC Registry cohort included patients who had a confirmed or suspected genetic condition that increased their risk of developing thoracic aortic aneurysm. Enrollment data were gathered from medical records or patient interviews. Electronic health records contributed to the information database, and DNA, plasma, lymphocytes, and surgical tissue were added to the Biospecimen Repository. Every two years, researchers used medical information to gather new data, and they collected new images. Images were read centrally by the Imaging Core, and diagnosis was confirmed by the Phenotyping Core. Follow-up data was collected at regular intervals for more than 2,600 patients, with the interval varying by the diagnosis.

Read more about enrollment criteria and participating centers in the GenTAC Registry.

More Information

In order to enroll in the Registry, participants were required to have one of the following conditions:

  • Bicuspid aortic valve with coarctation
  • Bicuspid aortic valve with family history of thoracic aortic enlargement
  • Bicuspid aortic valve without known family history of thoracic aortic enlargement
  • Ehlers-Danlos syndrome
  • Familial Thoracic Aortic Aneurysm and Dissections
  • FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 genetic mutation
  • Loeys-Dietz syndrome
  • Marfan syndrome
  • Shprintzen-Goldberg syndrome
  • Turner syndrome
  • Other aneurysms and dissections of the thoracic aorta under age 50 not due to trauma
  • Other congenital heart disease (e.g., Tetralogy of Fallot, coarctation)

The NHLBI and NIAMS co-sponsored the GenTAC Registry. Collaborators included the National Marfan Foundation, the Turner Syndrome Society of the United States, the Ehlers-Danlos National Foundation, and the Ehlers-Danlos Syndrome Network C.A.R.E.S., Inc. The GenTAC Registry consisted of eight clinical centers, an Imaging Core, a Phenotyping Core, and a Data Coordinating Center.

Clinical Centers

  • Baylor College of Medicine
    Scott LeMaire, M.D., Principal Investigator
    Irina Volguina, M.D., Ph.D., Project Manager

  • Johns Hopkins University School of Medicine
    William Ravekes, M.D., Principal Investigator
    Harry C. Dietz, M.D., Investigator
    Kathryn Holmes, M.D., M.P.H., Investigator, Oregon Health and Sciences University
    Margaret Li, Research Coordinator

  • National Institute on Aging at Harbor Hospital
    Nazli B. McDonnell, M.D., Ph.D., Principal Investigator
    Ben Griswold, Study Coordinator

  • Oregon Health & Science University
    Cheryl Maslen, Ph.D., Principal Investigator
    Howard Song, M.D., Ph.D., Investigator
    Michael Silberbach, M.D., Investigator
    Alisha Berry, Study Coordinator

  • Queen's Medical Center
    Ralph V. Shohet, M.D., Principal Investigator
    Fiona Kennedy, R.N., Research Nurse Coordinator

  • The University of Pennsylvania
    Reed E. Pyeritz, M.D., Ph.D., GenTAC Principal Investigator
    Joseph Bavaria, M.D., Investigator
    Karianna (Rita) Milewski, RPh, M.D., Ph.D., Investigator

  • Weill Cornell Medical College of Cornell University
    Richard Devereux, M.D., Principal Investigator
    Jonathan W. Weinsaft, M.D., Investigator
    Mary J. Roman, M.D., Investigator
    Grace Malonga, M.P.H., Clinical Research Coordinator

  • University of Texas Medical School at Houston
    Scott LeMaire, M.D., Principal Investigator
    Shaine Morris, M.D., Investigator

  • Data Coordinating Center, RTI, International
    Barbara Kroner, Ph.D., M.P.H., Principal Investigator
    Tabitha Hendershot, Senior Project Manager
    Kevin Wilson, M.S., M.P.H., Systems Analyst
    Liliana Preiss, M.S., Statistician

  • Imaging Core at MedStar Health Research Institute in Washington, D.C.
    Federico Asch, M.D., Principal Investigator
    Neil Weissman, M.D., Co-Principal Investigator
    M. Therese Tupas-Habib, Manager

  • Phenotyping Core at Johns Hopkins University
    Jennifer Habashi, M.D., Principal Investigator
    Gretchen Oswald, M.S., C.G.C., Genetic Counselor

How does the GenTAC Alliance work?

The GenTAC Alliance aims to promote data sharing and research to improve outcomes for people who have thoracic aortic disease. Although the management of thoracic aortic aneurysms has improved significantly, patients with aortic dissections or tears, rupture, or other acute complications of thoracic aortic aneurysms continue to have high burden of disease. Ruptures and dissections of thoracic aortic aneurysms remain a major cause of death in this population.

The Alliance is now working to maintain and expand collaborations, provide leadership, enhance the scope of research for genetically triggered thoracic aortic conditions, promote education about these conditions, enhance patient care through education and research, recruit patients for clinical trials, and develop a pilot grant program for young investigators. The Alliance will also enhance the quality and capabilities for federal and private grant applications for these rare diseases that challenge cardiovascular medicine.

The GenTAC Alliance members will include representatives of the NHLBI, registries from the GenTAC Registry, other related registries, and patient advocacy organizations. Prospective members also include scientists, clinicians, foundations, universities, and more.