Patient case: 45-year-old female with Melanoma. Genetic variant: BRAF (V600E), CDKN2A Deletion. Other conditions: None.

Clinical trial: Screening for Alpha Thalassemia in Healthy Volunteers

Summary: Background:
  Alpha thalassemia is a blood disorder. It is caused by genetic deletions. Part of the DNA is missing from a group of genes called alpha globin. Alpha thalassemias are some of the most common genetic deletions. We are testing for alpha thalassemia trait. Alpha thalassemia trait is when someone has only two out of the normal four alpha globin genes. In some people, they lead to no symptoms. Others have changes that lead to disease, including mild anemia. Researchers want to learn more about alpha thalassemia and blood vessels. This may allow them to develop new treatments for blood diseases such as sickle cell disease.
  Objective:
  To better understand how alpha globin deletions in healthy people affect blood vessels.
  Eligibility:
  Healthy volunteers ages 18 40 who self-report African ancestry.
  Design:
  Participants will provide a one-time saliva sample. This can be by mail, in-person at a study event, or at NIH.
  Participants will get a small kit to collect their saliva sample. The kit has easy instructions. The sample does not need to be put in the refrigerator.
  Participants will spit a small amount of saliva (less than half a teaspoon) into a collection tube.
  Participants will close the funnel lid tightly, and then unscrew the funnel lid from the tube. They will then close the tube tightly with the small cap provided and shake the tube for 5 seconds.
  Participants will place the tube in the provided envelope and mail it to NIH. The specimen will be stored and processed in the lab.
  Participants may be invited to participate in more research studies, whether or not researchers find that they have alpha thalassemia trait.

Detailed description: Many of the complications of sickle cell disease, such as stroke, kidney damage, skin ulceration,pulmonary hypertension, and cardiac hypertrophy are prevented, delayed or reduced by inheritance of one of more deletions of the alpha globin genes. Our long-term research goal is to understand how deletions of alpha globin protect against the vascular complications of sickle cell disease.
  Deletions of alpha globin are common and found in approximately 5% of the world s population.They are especially common among Africans and people of African ancestry, as well as in India, China, and the Pacific Islands, where prevalence can range from 5 - 80%. A single deletion has little effect on the red blood cell, but two deletions can give rise to alpha thalassemia, a mild microcytic anemia. Patients with sickle cell disease who have two alpha globin deletions tend to have a higher hemoglobin level, smaller red blood cells, and a lower fraction of circulating reticulocytes consistent with decreased hemolysis and red cell turnover. They also have a lower number of dense or irreversibly sickled cells. These changes might explain why alpha globin deletions reduce the severity of sickle cell disease.
  However, a novel function for alpha globin as a regulator of endothelial nitric oxide (NO) has recently been identified that raises new questions about how alpha globin deletions protect against sickle cell disease. We hypothesize that individuals with two alpha globin deletions will have decreased gene expression and protein levels of alpha globin in vascular endothelium, permitting more NO to diffuse across the myoendothelial junction, compared to individuals who have all four alpha globin genes intact. In this protocol we will screen healthy volunteers to identify those with two alpha globin deletions; these individuals as well as matched controls will be referred to a separate protocol to undergo studies of vascular endothelial function.

Eligibility: -  INCLUSION CRITERIA:
  Subject report of the following:
  1. Age 18 - 50
  2. Self-report of African ancestry
  3. Willingness and legal ability to give and sign informed study consent
  EXCLUSION CRITERIA:
  There are no exclusion criteria for this screening protocol

Relevance to patient case: not relevant