Do I Want to Know?

by Ken C., Indiana, age 14

Several years ago, my dad’s mom had to have an eye removed because of a tumor. She later found out that she had several cysts on her spinal cord and even more tumors in her kidneys. She died a couple of years after giving birth to my dad. She had no idea that she had a rare inherited disease. Unfortunately, my dad inherited the disease and there was no way of knowing, until recently, if I had inherited it also.

The disease that my dad could pass on to his children is called von Hippel-Lindau, or VHL. VHL is an autosomal dominant disease, which means, each child has a 50-50 chance of inheriting it from a parent. VHL can cause cysts and/or tumors to form in the eyes, brain, spine, kidneys, pancreas, endo-lymphatic sac and adrenal glands. There is currently no cure for VHL, so the best way to fight this disease is to closely monitor all of the areas that it can affect. My parents sent me for testing on an annual basis, and as I got older they wanted me to add an MRI of the brain and spine and a CAT scan of the abdomen, along with blood and urine tests. These tests can be very costly when done every year or two for your entire life, not to mention stressful. An alternative to the yearly monitoring is to have a DNA test to determine if you have inherited the mutated gene. If not, there is no need for monitoring.

In order to have the DNA test done, my dad had to have the test completed first. My dad had a blood sample taken and it was sent to the laboratory at the University of Pennsylvania. Once they found the mutated gene, I could submit a sample to the same lab and they could compare my DNA to his. They would look at the same place on the DNA where they found his mutated gene and see if my DNA also contained the mutation.

The decision to have the DNA test was a difficult one. I do not like to have my blood drawn, so I really did not want to have a sample drawn. I had heard on television about DNA tests being done from a cheek swab and had my parents find out if it was possible to have a sample taken that way.

After asking many people, my parents found out that the doctors could still read the DNA, and tell if I had the disease, from a cheek swab. (See also following article.) Once we found this out, I had to decide if I really wanted to know if I had the disease or not. I debated in my head if I wanted to know, or if I wanted to continue having the screenings done every year. I also had to consider how I would feel if I found out that I didn’t have VHL, but my sister did; or how I would feel if I did have it and my sister didn’t. After awhile, I decided to have the test done. I had my parents schedule an appointment.

Early one January morning, my mother drove me to the Indiana University (I.U.) Department of Genetics downtown. This is where I met with the genetic counselor, Cindy Hunter. I had to meet with the counselor so she could explain what VHL is, how it is inherited, how they would obtain the sample, how they would test the sample, and how the results would be returned. She asked me if I had any questions about VHL, the test method, or what the test results would say. Once I had all my questions answered, she called the geneticist, Dr. Gail Vance.

When Dr. Vance arrived, she gave me a more in-depth explanation of the test. She also informed me of what utensils would be used to extract the tissue sample. She showed me an example of the swab that would be used. She explained that she would send the swab to a laboratory in Pennsylvania that would perform the test on the tissue sample to find out if I had the disease. When she finished, she called my mother into the room and told us both that we would need to come back at a later date to have the test performed. Dr. Vance explained that they prefer to have the patient return after they have a chance to think about the information that they have been given. Sometimes people will decide not to return to have the test done.

After a few months, we went back to the I.U. Department of Genetics to have the test done. Cindy Hunter called me back to the exam room and asked if I had any questions before we did anything. I did not have any questions, so she opened the test kit. She handed me the swab and told me to scrape the side of my cheek with the brush-like end of the swab. Cindy reminded me that I really needed to scrape hard or there would not be enough tissue for the doctors in Pennsylvania to get the results. I scraped my cheek as hard as I could with the swab, without breaking it. After I was done scraping, I gave the swab back to her. She put it in a tube and told me she would mail it to the lab. Once the kit was sealed, she called my mother in and told us that the results should be returned to them in about two to three weeks.

About three months after the sample was mailed, we finally got a call from the genetic counselor saying that the results were in. My mother drove me downtown one more time. Cindy was waiting on us and she called both of us into the room. The doctor and the counselor both were in the room. They asked us if we had any questions and asked if I still wanted to hear the results. I was pretty anxious, so all I wanted to hear was whether I had the disease or not. Since neither of us had any questions, the doctor got out the paper and started to read. The paper stated that the laboratory did not find the VHL genetic mutation in the sample that was sent to the lab. In other words, it said the result was negative.

Knowing that I do not have VHL is a huge relief. Going to the genetic counselor and having the test done have really taught me a lot. It helped me understand the disease that my dad has a lot more than anything else before. It also helped me understand just a little bit better what my dad goes through every time he has to wait for the results on a CAT scan or an MRI. It helped me the most though in that it made me realize that I’m really happy I don’t have to deal with VHL. I’m very pleased that I decided to have the DNA testing done.

Cheek Swab DNA Test

Cheek brush samples can not be used for all mutations. They are fine for single base (point) mutations detected by DNA sequence analysis, but are not useful for partial or complete deletions that are detected by Southern blot analysis. Cheek brush samples do not yield enough DNA, nor do they yield the large pieces of DNA needed to perform Southern blot analysis. In the future, we may be implementing a PCR based assay for deletions (much like that reported by the French group at the meeting in Padua) which will get around our current need for large amounts of big DNA fragments.

Meanwhile, it is safe to assume that the first analysis in a family will require bloods drawn, and can not be done with only a cheek swab. Once that first mutation has been identified, depending on the nature of the mutation found, cheek swabs may be sufficient for subsequent tests in a family. Please inquire to determine what is required for your family.