What is a genetic test for PXE?

A genetic test is a laboratory test that may be able to tell if you have changes called mutations in the gene associated with PXE, the ABCC6 gene. If the test finds that you have two changed copies of the gene (mutations or alterations), then you are affected by PXE. If the test finds only one changed copy of the gene, then either you are a carrier, or you are affected, but the test at this stage of its development is unable to uncover your second mutation. If the test finds that you have no mutations, then it is very likely you don´t have PXE, or the test, at this stage of its development, could not find either of your mutations. There are some mutations and alterations that have not yet been discovered by researchers.

Return to top

Deciding to be tested is a personal decision that should be made after consulting your family and healthcare providers. You might choose genetic testing for the following reasons:

To intervene medically: People at a higher risk for PXE symptoms may have the option of having more frequent clinical exams, screening tests, avoiding specific risk factors, making lifestyle changes to lessen additional risk, or taking preventive measures, if available.

To relieve anxiety: If a person has multiple family members who have PXE that can be traced to specific genetic mutations, then a negative test result (meaning there are no mutations) or confirming only a carrier status may give this person a sense of relief.

Return to top

Testing may cause depression, anxiety, or guilt. If a person receives a positive test result (meaning at least one mutation exists), it may cause anxiety or depression about the possibility of developing PXE. Some people may start to think of themselves as sick, even if they never develop PXE symptoms. If a person does not have the mutation when other members of the family do, this individual may experience guilt.

Testing may cause family tension. In some situations, a person may feel a responsibility to tell extended family members that they have a positive test result and encourage them to be tested. This process may lead to tension in the family.

Testing may provide a false sense of security. Just because a person's genetic test result is negative (meaning no mutation was found) does not mean that person will never develop PXE symptoms. It is possible that the test at this stage of its development could not find either of your mutations.

Testing may provide unclear results. A person's gene may have a unique mutation that has not yet been discovered, and so its meaning is unknown. Or, the gene may have a mutation that is not detected by the genetic test. This may lead to anxiety and uncertainty.

Testing may be costly. Genetic testing and counseling can be expensive, especially if it is not covered by insurance. Some people pay for testing "out of pocket" because they want complete privacy when testing for PXE.

Testing may raise confidentiality concerns. Results of genetic tests may be placed in a person's medical record, where there is a chance that this information could be passed on to insurance companies, managed care organizations, or employers. Some people fear that their test results may lead to genetic discrimination. Many people who undergo genetic testing are concerned about maintaining the privacy of their genetic information. They may be unsure if they want to share test results with immediate relatives and are concerned about employment and health insurance discrimination, which could result in the loss of a job and/or insurance coverage.

Another limitation of genetic testing involves the meaning of these various mutations. We have not yet determined if or how the different mutations (changes) in the ABCC6 gene (genotype) are associated with the symptoms (phenotype). We have collected information from over 600 individuals about their PXE phenotype. We looked at genotypes and phenotypes and could not find any direct association. In other words, we could not link a specific gene mutation to a specific symptom of PXE. We do know that environmental factors, such as lifestyle and diet, can have a tremendous impact on the symptoms and progression of PXE. It is also possible that other genetic factors such as “modifying genes” may affect how severe PXE is or what organs it affects. The genetic test for PXE does not test for these other factors.

Therefore, a genetic test will not be able to tell what symptoms of PXE will appear or when they will begin. The test results cannot tell you how severe the condition will be or how it will progress over time.

What does the test cost and how shall you pay for it?
The price of the test varies compared to how much work needs to be done to find the mutations in your genes. It is easier to find one of the common mutations than it is to find a mutation that is unique to you. Likewise, if you know the mutations of a family member, the test costs less since GeneDx will be looking in a specific location for just two mutations. The costs are detailed in the Cost of the Genetic Test for PXE box below.

Cost of the Genetic Test for PXE GeneDx http://www.genedx.com/services/dis_pxe.php Price and turn-around time: Fees are subject to change without notice. Testing for common mutations in a new patient ..................................... $500 Approximately 2-4 weeks Testing for other than common mutations in a new patient ................. $3000 Approximately 8-10 weeks Testing of a relative for one specific known mutation.............................. $350 Approximately 2-4 weeks Testing of a relative for two specific known mutations ........................... $500 Approximately 2-4 weeks Prenatal diagnosis for a specific known mutation .................................$1500 Approximately 2 weeks

You can call PXE International for a free phone consultation with our board certified genetic counselor at 202.362.9599. The counselor will help you understand what it means to be tested. Once you have all of your questions answered, you can make an informed decision about whether or not to be tested. Once you determine that you are interested in testing for PXE, you will want to get preauthorization from your insurance company. The test can be quite expensive. You are permitted to pay out of pocket, if you wish, but you still must have a healthcare professional order the test for you. You may order the test through our genetic counselor if you are going to pay out of pocket.

You will find a sample letter for requesting insurance preauthorization on this site, or on the GeneDx site (http://www.genedx.com/services/dis_pxe.php).

2) You have skin lesions that look like those associated with PXE, but you do not have eye findings, and 1) you have a “negative” or uncertain skin biopsy, or 2) you would rather not have a skin biopsy. A genetic test can confirm the diagnosis of PXE. However, if the test comes back negative, it is possible that it just did not find your mutations.

3) You have peau d´orange, angioid streaks and/or retinal bleeding, but do not have skin lesions. As above, a genetic test can confirm the diagnosis of PXE. However, if the test comes back negative, it is possible that it just did not find your mutations.

4) You have a sibling with PXE. If you have a sibling with PXE, you have a 50% chance of being a carrier (having one mutation), a 25% chance of actually having PXE (having two mutations), or a 25% chance of having no mutations, and therefore not being a carrier, or being affected by PXE. (See How is PXE Inherited?.) If your sibling´s mutations are known, then a genetic test can easily find the same mutations in you, if they are present. If your sibling´s mutations are not known, the test may or may not tell you if you have PXE. If two mutations are found in your sample, then you are affected. If one mutation is found, it is likely you are a carrier, but it also may be that your other mutation was not discovered. If no mutations are found, perhaps you are not a carrier or are not affected, or the test did not discover your mutations. If you are at least 20 years old (and younger for many individuals), then it would be easier and less expensive to get an eye examination to determine if you have angioid streaks. If you do have angioid streaks and you have an affected sibling, then you probably have PXE.

5) You have a parent with PXE. If one of your parents has PXE, you are a carrier. In the unusual event that your other parent is a carrier, then you could be either a carrier or affected. If your parent´s mutations are known, then a genetic test will tell you with certainty if you are a carrier or affected. If your parent´s mutations are not known, the test may or may not tell you if you have PXE. If two mutations are found, then you are affected. If one mutation is found, it is likely you are a carrier. If no mutations are found, then it is still possible that you are a carrier and the test at this stage of its development could not find the mutations.

Return to top

After you have received an approved preauthorization from your insurance company (try to get a written copy or fax), or determined that you will have to pay a co-payment, or pay for all of the test costs out of pocket, you need to get the right forms and have your blood collected.

Follow these steps:

1. Get the necessary forms: You need two forms, the Sample Submission Form and the Clinical Data Form. You can find these forms on this site, or online at the GeneDx site (http://genedx.com/services/dis_pxe.php).

2. Fill out the forms: Bring the Sample Submission Form and the Clinical Data Form to your doctor. You should fill out the Clinical Data Form together with your doctor and send it and the Sample Submission Form to the laboratory with your sample. If it is possible for you, we would like you to fill out the Clinical Data Form online.  To do this, please request an ID and Password for the online form from the PXE International office by emailing info@pxe.org or by calling 202.362.9599.

3. Sample collection: Your doctor can collect a blood sample from you for genetic testing. Or, if you would rather, you can use a cheek swab kit. You can order a cheek swab kit from GeneDx or PXE International or your doctor can order the kit and have it mailed to you.

GeneDx will look at the ABCC6 gene in your DNA and determine if there are any mutations in the gene. GeneDx will send a report to your doctor and s/he will report the results back to you. You can ask your doctor for a copy of the report, and you can also make an appointment with our board certified genetic counselor by calling 202.362.9599 and leaving your name, address, email and phone number and whether you would like a daytime or evening phone appointment.

When the genetic test involves only a cheek swab, there are no significant physical risks beyond those of rubbing a swab on the inside of your cheek. If it involves a blood draw, you might experience slight pain and bruising. There is also the possibility that finding out the results of a genetic test could affect you emotionally. Finding out that you do or do not carry PXE mutations can be emotionally difficult. You may feel confused or upset about being diagnosed with PXE. You may even experience some feelings of guilt and anxiety if you were to discover that you don´t have PXE while a relative does.

Another risk to consider before undergoing genetic testing is the privacy of your test results. People may be concerned that they will lose their job or be unable to get health or life insurance if someone learns that they carry the mutated
gene(s) for PXE. Federal legislation to ban genetic discrimination in employment and insurance is working its way through Congress. Already established, the Americans with Disabilities Act (ADA) protects Americans with disabilities from discrimination. In addition, many U.S. states prohibit health insurers from asking for or requiring genetic test results, from denying coverage on the basis of genetic tests, and from using tests to determine rates and benefits.