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DNA Testing for VHL
How to Go About DNA Testing(from the VHL Handbook, 2012)
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 of a person with VHL. Each child of a person with VHL is at 50% risk for VHL. 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, and has been certified as compliant with the Clinical Laboratory Improvement Amendments (CLIA) in the United States, or has achieved equivalent quality ratings in other countries.
If DNA testing finds the altered VHL gene, the results are positive: yes, this person has VHL. If the DNA testing finds that both copies of the VHL gene are unaltered, the test is negative: this person is unlikely to have VHL. There is always some margin for error. In a CLIA-certified lab, the possibility of error is under 1–2%, which is considered to be as certain as it gets in nature.
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, sometimes including some additional testing to look for larger deletions. Properly done, 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 check for that same mutation in this second person’s DNA. This first test in the family becomes a road map for subsequent tests in that family.
People who were tested prior to the year 2000 using a method called “linkage analysis” may wish to be re-tested using DNA sequencing, or more modern methods, which 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 a little longer and cost a little more to get results from a complete screen. For people in this situation, it is important to choose a lab with experience with research teams studying VHL, that can provide a more thorough report.
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, check the genetic counselors’ website, http://www.nsgc.org. You can search by institution, country, or postal code. Large medical centers will usually have a department of “cancer genetics.” If so, this is the best place to assess your risk for VHL.
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.
The list of clinical testing labs offering complete testing for VHL (including large deletions) is maintained on the internet at http://genetests.org. The list of DNA testing labs with close relationships with research teams is maintained by VHLFA at http://vhl.org/dna/dna-src.php.
If your DNA diagnosis is unclear, please contact the VHL Family Alliance to discuss it further and to consider participating in a study to understand these situations. Contact info@vhl.org
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