Pathogenetic Basis of Aortopathy and Aortic Valve Disease
| Status: | Recruiting |
|---|---|
| Conditions: | Other Indications, Other Indications, Other Indications, Cardiology, Cardiology, Cardiology, Cardiology, Cardiology, Neurology, Orthopedic, Orthopedic, Orthopedic, Dermatology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Dermatology / Plastic Surgery, Neurology, Orthopedics / Podiatry, Other |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 8/10/2018 |
| Start Date: | December 2015 |
| End Date: | December 2028 |
| Contact: | Lindsey Elmore, BS, BA |
| Email: | lhelvaty@iupui.edu |
| Phone: | 317-278-3020 |
The main purpose of this study is to define the complex genetic and pathogenic basis of
thoracic aortic aneurysm (TAA) and other forms of aortopathy and/or aortic valve disease by
identifying novel disease-causing genes and by identifying important genetic modifiers for
aortic and aortic valve disease severity.
thoracic aortic aneurysm (TAA) and other forms of aortopathy and/or aortic valve disease by
identifying novel disease-causing genes and by identifying important genetic modifiers for
aortic and aortic valve disease severity.
Thoracic aortic aneurysm (TAA) is a type of aortopathy describing dilation of the proximal
aortic dimensions including the aortic root, which is a risk factor for aortic dissection and
sudden cardiac death. TAA and other forms of aortopathy (e.g. aortic tortuosity or aortic
hypoplasia/stenosis) develop in the presence or absence of additional cardiovascular
malformations including bicuspid aortic valve. TAA is associated with connective tissue
disorders (e.g. Marfan syndrome), and familial clustering has been identified in a
significant proportion of nonsyndromic cases, establishing high heritability. Pedigree
analysis of TAA kindreds clearly identifies complex inheritance; however, progress towards
understanding the genetic basis of TAA and other forms of aortopathy and, ultimately, the
susceptibility to aortic dissection remains incomplete. There is a clinical need to develop
novel methods for predicting disease risk based on genotype and phenotype, to further
elucidate the genetic and pathogenic mechanisms of aortopathy, and to improve medical and
surgical therapies. The overarching hypothesis of this study is that individual genetic
variation modulates susceptibility to disease severity and progression. The goals of this
study are 1) to ascertain a cohort of subjects who have aortopathy and/or aortic valve
disease including TAA or who have genetic risk for the development of aortopathy and/or
aortic valve disease, 2) to collect paired blood and tissue samples from well-characterized
subjects, family members of subjects, and controls to perform genome-wide DNA sequence,
histopathologic, transcriptional, and proteomic analyses, and 3) to establish a tissue
biorepository with detailed phenotype information to facilitate a broad spectrum of current
and future studies.
aortic dimensions including the aortic root, which is a risk factor for aortic dissection and
sudden cardiac death. TAA and other forms of aortopathy (e.g. aortic tortuosity or aortic
hypoplasia/stenosis) develop in the presence or absence of additional cardiovascular
malformations including bicuspid aortic valve. TAA is associated with connective tissue
disorders (e.g. Marfan syndrome), and familial clustering has been identified in a
significant proportion of nonsyndromic cases, establishing high heritability. Pedigree
analysis of TAA kindreds clearly identifies complex inheritance; however, progress towards
understanding the genetic basis of TAA and other forms of aortopathy and, ultimately, the
susceptibility to aortic dissection remains incomplete. There is a clinical need to develop
novel methods for predicting disease risk based on genotype and phenotype, to further
elucidate the genetic and pathogenic mechanisms of aortopathy, and to improve medical and
surgical therapies. The overarching hypothesis of this study is that individual genetic
variation modulates susceptibility to disease severity and progression. The goals of this
study are 1) to ascertain a cohort of subjects who have aortopathy and/or aortic valve
disease including TAA or who have genetic risk for the development of aortopathy and/or
aortic valve disease, 2) to collect paired blood and tissue samples from well-characterized
subjects, family members of subjects, and controls to perform genome-wide DNA sequence,
histopathologic, transcriptional, and proteomic analyses, and 3) to establish a tissue
biorepository with detailed phenotype information to facilitate a broad spectrum of current
and future studies.
Inclusion Criteria:
- Open to external enrollment:
- Subjects with a genetic diagnosis of Marfan Syndrome (MDS), Loeys-Dietz Syndrome
(LDS), or Vascular Ehlers-Danlos Syndrome (EDS); (Positive genetic testing or a
previous cardiac study required to be eligible)
- Family members of eligible subjects (Only family members of subjects with
syndromic diagnoses are eligible for external enrollment at this time)
- Closed to external enrollment:
- Subjects with aortic disease including TAA* or dissection, aortic tortuosity, or
aortic hypoplasia/stenosis (based on any cardiac imaging modality including
echocardiography, CT, MRI, or angiography)
- Subjects with aortic valve disease (bicuspid, unicuspid, or tricuspid disease)
- Control subjects having tissue removed during a surgical procedure (e.g. coronary
artery bypass graft surgery (CABG), cardiac transplant, etc.)
Exclusion Criteria:
• Inability or unwillingness to provide consent (assent when indicated)
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