|
 |
DNA Testing for VHL
How to Go About DNA Testing(from the VHL Handbook, 2005)
Anyone with a first- or second-degree relative with VHL is "at risk" for VHL. First degree relatives are parents, children, sisters, and brothers. Second-degree relatives are cousins, aunts, uncles, grandparents, and grandchildren. The only way to determine for sure whether someone has VHL is through DNA testing. This is a blood test that must be processed at a clinical testing laboratory (lab) that has the necessary equipment and reagents to test for VHL.
If DNA testing finds the altered VHL gene, we say that the results are positive: yes, this person has VHL. If the DNA testing finds that both copies of the VHL gene are unaltered, we say that the test is negative. This person is unlikely to have VHL. There is always some margin for error. When the possibility of error is under 1-2%, it is considered to be as certain as it gets in nature. If the margin for error is 15%, you may wish to have additional testing.
Anyone at risk for VHL who has not received a negative DNA test result should continue to follow a conscientious screening program to ensure early diagnosis of any VHL problems.
To initiate DNA testing in a family, a person in the family with a clinical diagnosis of VHL, working through a geneticist or genetic counselor, should submit a blood sample for testing. The lab will check to see that they can determine the alteration in this person by performing a complete screen of the VHL gene. This test is greater than 99% successful in finding mutations in patients with a germline mutation in the VHL gene. Once a mutation has been found, the exact change in this person's VHL gene will be the same alteration that is passed within this family. Now another person in the same family who does not have a clinical diagnosis of VHL can submit a blood sample, and the lab can go directly to that position and check for that same mutation in this second person's DNA. This first test in the family becomes a road map for the second test.
People who were tested prior to 2000 using a method called "linkage analysis" may wish to be re-tested using DNA sequencing or Southern blot analysis. These improved techniques are significantly more reliable. There have been situations where the results of linkage analysis have proven not to be correct.
For people who are the first in their families to be diagnosed with VHL, or for adoptees or others who do not have known blood relatives to assist in the testing, it can take 4 to 6 weeks or more to get results from a complete screen. For people in this situation, it is important to choose a lab with a high "hit rate" or level of success in finding mutations.
It is important to initiate DNA testing through a geneticist or genetic counselor, to ensure a thorough discussion of the personal impact of the results, whether they are positive or negative, and the possible insurance ramifications. To find a geneticist or genetic counselor, begin with your doctor or with the medical center where you normally go. Ask if they have a department of "cancer genetics." If so, this is the best place to assess your risk for VHL. If not, inquire in the departments of obstetrics, medicine or pediatrics. If they do not have an associated geneticist, they will know where to find one acceptable to your health plan.
If a mother-to-be is having any genetic testing done, she may request a VHL test be part of that scope of tests, especially if there is any VHL in the family at all, or any history of VHL-related tumors in other family members. Prenatal test results are usually part of the mother’s medical record, not the child’s. Ask to be sure.
The complete list of clinical testing labs offering testing for VHL is maintained on the internet at http://www.vhl.org/dna/dna-src.php. As of the date of publication of this booklet, the labs with the highest "hit rates" are those in Philadelphia, Pennsylvania; Padua, Italy; Saõ Paolo, Brazil; Ingelheim, Germany; and Lyon, France.
Catherine Stolle, Ph.D., FACMG
Dr. Hans-Jochen Decker
Dr. Sophie Giraud, Laboratoire de Génétique
Dr. Alessandra Murgia Via Giustiniani 3 35128
|
| Contact Us | Copyright 1993-2012 |