Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension

Test group:

The study will include two visits for the test group:

At visit one there will be required and optional research activities as the following:

Required research activities:

-Peripheral blood draw (3.5 tablespoons) drawn by research coordinator. This blood is to isolate PBMCs for generation of iPSCs.If patient did not want to give a blood sample we will ask if willing to give a urine sample. A clinical research coordinator will give the patient a plastic container and will explain how use it.

The following research activities will be optional at visit one:

• Physical exam and blood work (kidney/liver, blood count, coagulation, B-HCG, iron studies, and plasma for microRNA) processed at Presby Lab. This will be required if the patient approved to do right heart cath.
• Electrocardiogram.
• 6 Minute Walk Test.
• Skin Biopsy from underarm or inner thigh by physician (Dermatology department) (if patients agree to do, if not, we will only get a blood sample)
• Resting Echocardiogram

This visit will last 7-8 hours.

Study Visit Two:

This will include optional Right Heart Catheterization.

• Right Heart catheterization by PI/Sub-Investigator. Duration ~ 3 hours

• IF the results show that the pressure in the lung vessels is elevated without exercise AND there is no other abnormality in the heart function, we will NOT do exercise testing.
• IF the patients are physically able to perform exercise testing/agree to do an exercise testing, patients will have an Exercise Right Heart catheterization and a Rest and Stress Echocardiography. (Determined by PI/Sub-Investigator
• All participants who will do right heart catheterization will have to do a pregnancy test before the procedure.
• Exercise Echocardiogram completed in. If patient unable to exercise medication (Dobutamine) will be given. Duration ~ 1-2 hours
• Exercise Right Heart catheterization Duration ~ 2-3 hours

CONTROL GROUP

Control group will only have one visit. At this visit there will be a minimum required research activity to participate in the study and this will include:

-Peripheral blood draw (3.5 tablespoons) drawn by research coordinator. This blood is to isolate PBMCs for generation of iPSCs. If participant did not want to give a blood sample we will ask if willing to give a urine sample.

The following research activists will be optional at visit one:

• Physical exam and blood work (kidney/liver, blood count, coagulation, B-HCG, iron studies, and plasma for microRNA) processed at Presby Lab. This will be required if the patient approved to do right heart cath.
• ECG, done by research coordinator and read by PI/Sub-Investigator.
• 6 Minute Walk Test, done by research coordinator, if patient could perform.
• Skin Biopsy from underarm or inner thigh by physician (Dermatology department) (if patients agree to do, if not, we will only get a blood sample) This visit will last 6-7 hours.

Inclusion criteria

for Test Group:

• Consenting individuals age 18-60 years of age
• Have a confirmed genetic homozygous mutation (including ISCU1/2, FXN, BOLA3, NFU1) that causes the impairment of iron-sulfur cluster formation; such a subject will not be excluded from this study even if that patient's first degree relative(s) does not enroll in this pilot study.

Inclusion criteria

for Control Group:

• Consenting individuals age 18-60 years of age
• First degree family member (mother, father, sister, brother, son, or daughter) of recruited individual in the test group
• Have a confirmed heterozygous genetic mutation (including ISCU1/2, FXN, BOLA3, NFU1)

Exclusion criteria

for Test and Control Group:

• Impaired decision making capacity
• Inability to consent to procedures
• Children less than 18 years of age and adults older than 60 years of age
• Current pregnancy