Patient case: 63-year-old female with aortic aneurysm; genetic feature: ACTA2

Clinical trial: Vascular Disease Discovery Protocol

Summary: Background:
  Some genetic diseases put increase the risk of heart and blood diseases, which are the number one cause of death and disability in the U.S. Researchers want to study diseases of the heart and/or blood vessels. They want to collect data and specimens from affected people, their family members, and healthy people.
  Objective:
  To study diseases of the heart and/or blood vessels.
  Eligibility:
  People age 2 and older who may have genetic disease affecting the heart and/or blood vessels Their relatives
  Healthy volunteers
  Design:
  Participants will be screened with a medical history, physical exams, and imaging tests. Participants may have a few visits or visits for 2 weeks or more. This will depend on their age and disease status. Visits may include:
  Photographs of the face and body
  Heart tests
  Samples taken of blood, urine, saliva, skin, and/or tissue
  Scans. For some, a dye may be injected into a vein.
  A six-minute walk test
  Lung tests. For some, participants will blow into a tube. For others, they will breathe in a gas from a mask, have a small injection, then have a scan.
  Stress tests while walking on a treadmill or riding a stationary bike
  Ultrasound of veins and arteries
  Devices outside the body testing the stiffness and function of arteries
  Eye exam and eye tests. For some, a dye may be injected in a vein.
  Blood pressure tests
  Measurements of blood flow under the skin and in the arms and fingernail blood vessels
  Devices outside the body testing flexibility of the blood vessels and skin, and skin temperature...

Detailed description: The NIH provides a unique opportunity for research scientists to participate in the bench-to-bedside process, which is essential for the full implementation of translational medicine programs. The study of rare monogenetic and undiagnosed diseases is a complex bedside-to-bench-to-bedside endeavor. Recent studies show that rare genetic variants are more likely than common variants to have deleterious effects on protein structure, function, and/or expression, possibly leading to clinically relevant events. Studies of large patient populations offer the opportunity to identify rare genetic variants underlying human disease and will have impactful implications for human health. We propose to characterize the etiology and natural history of rare and orphan diseases with vascular phenotypes. We will also study rare genetic modifiers and identify novel disease mechanisms contributing to common vascular diseases. Subsequent disease-related protocols may be developed based on findings from subjects enrolled in this protocol for further intensive natural history studies and potential innovative therapeutic studies. In addition to its role in investigating individuals who are of interest to the Translational Vascular Medicine Branch (TVMB) of the NHLBI, this protocol can provide a possible avenue for admitting subjects from other NIH programs, such as the NIH Undiagnosed Diseases Program, the Center for Human Immunology Trans-institute program or other NIH protocols where subjects exhibit vascular phenotypes.

Eligibility: -  INCLUSION CRITERIA:
  -  Affected or unaffected adult and child cohorts (including genetic carriers or non-carriers as reference biospecimen) are eligible.
  -  Pregnant and nursing women are eligible to participate in this study if they have been referred with a known or suspected pathology, if they are a relative of an index case with a known or suspected pathology.
  -  Healthy pregnant and nursing women may participate as healthy volunteers for minimal risk procedures
  -  Healthy adult volunteers must be 18 years of age or older, must agree to have blood or tissue samples studied and potentially stored for future research.
  -  Unaffected and unrelated children above 2 years of age are eligible to participate in this study as healthy volunteers
  EXCLUSION CRITERIA:
  -  Healthy volunteers unable to give informed consent or who decline to have blood drawn and/or tissue studies or who do not consent to have samples stored for future research may be excluded from this study.
  -  Healthy volunteers who are pregnant or nursing will be excluded from procedures that would expose them to more than minimal risk as well as to radiation exposure.
  -  Cognitively impaired individuals who are not affected or not related to affected subjects.

Relevance to patient case: not relevant