Genetic Testing and PXE
- What is a genetic test for PXE?
- Why choose genetic testing?
- Limitations of genetic testing
- Risks of genetic testing
- Reasons you may consider genetic testing - and our thoughts
- What does the genetic test cost and how do I pay for it?
- Okay, you want to be tested
Genetic counseling through PXE International
A genetic test is a laboratory test that may be able to tell if you have changes or alterations called mutations in the gene associated with PXE, the ABCC6 gene. You provide to the laboratory either a blood sample or a cheek swab sample. If the laboratory test finds that you have two changed copies of the gene, 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.
Read about the development of a rapid, reliable genetic test for PXE.1
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Choosing to be tested is a personal decision that should be made after consulting your family and healthcare providers, and even a genetic counselor. 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.
You might choose genetic testing to:
Intervene medically: People at a higher risk for PXE symptoms may have the option of having more frequent clinical exams or screening tests, avoiding specific risk factors, making lifestyle changes to lessen additional risk, or taking preventive measures if available.
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 confirmation of only a carrier status may give this person a sense of relief.
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Undiscovered mutations: All of the changes in the ABCC6 gene that cause PXE have not yet been discovered. GeneDx, the genetic testing laboratory which performs the test, first looks for certain common mutations in the gene. If you do not have one of these mutations, GeneDx will look next for a change elsewhere in the gene. If no changes are found, it is possible that the test is inconclusive. This can be confusing if you have symptoms of PXE or if you have been diagnosed based on an eye exam or skin biopsy. It is important to remember that you may have a change in the ABCC6 gene that is not yet discovered using the laboratory test that is available today. If you choose testing, we will work to help you understand whatever results you receive.
Meaning of mutations: Another limitation of genetic testing involves the meaning of these various mutations. We have not yet determined if or how the different mutations or 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.
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Physical risks: 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.
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 can 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: Many people who undergo genetic testing are concerned about maintaining the privacy of their genetic information. 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. 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.
The Genetic Information Nondiscrimination Act of 2008 (GINA) is a federal law that protects individuals from genetic discrimination in health insurance and employment. Genetic discrimination is the misuse of genetic information. The Americans with Disabilities Act (ADA) of 1990 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.
1) You have a positive skin biopsy (a biopsy that was stained and revealed fragmented elastic fibers, typical skin lesions), and angioid streaks.
You don´t need a genetic test, since the diagnosis of PXE can be made with certainty through the biopsy results.
2) You have skin lesions that look like those associated with PXE, but you do not have eye findings, and
a) you have a “negative” or uncertain skin biopsy, or
b) 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.
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Cost of the genetic test for PXE through GeneDx: The price of the genetic test for PXE varies compared to how much work must 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. Prices and turn-around times are listed below. Fees are subject to change without notice.
Testing for common mutations in a new patient
Approximately 2-4 weeks
Testing for other than common mutations in a new patient
Approximately 7-8 weeks
Testing of a relative for one specific known mutation
Approximately 2-4 weeks
Testing of a relative for two specific known mutations
Approximately 2-4 weeks
Prenatal diagnosis for a specific known mutation
Approximately 2 weeks
Insurance preauthorization or out-of-pocket: Once you determine that you are interested in the genetic test for PXE, you should get preauthorization from your insurance company. Please note that GeneDx does not provide Direct-to-Consumer testing. All tests must be ordered and results sent to a health care provider, usually a physician or genetic counselor. You may 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 PXE International's genetic counselor if you are going to pay out of pocket. Please call 202.362.9599 to make an appointment to speak with our board certified genetic counselor.
Here is a sample letter for requesting insurance preauthorization.
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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.
1. Complete the necessary forms: GeneDx has four forms on their PXE testing page available for download. Three are from GeneDX and one, the Clinical Data Form, is from PXE International. Some forms are for informational purposes only while others are required. All forms are available on the GeneDx website here:
- Test Requisition (or Sample Submission) Form: This form is required by GeneDx to perform genetic testing. Download it from the GeneDx website and complete it with your doctor at the time you request the genetic test.
- Informed Consent: You are not required to send GeneDx a completed consent document according to the federal regulations governing clinical laboratories. It is provided for your convenience. It is important to know that your state government may require documentation of the informed consent process. In addition, although GeneDx does not require the consent form to accompany the sample, GeneDx recognizes that the informed consent process is an important component to any genetic testing protocol and encourages practitioners to obtain informed consent from patients being tested.
- Test Info Sheet: This form provides information about the ABCC6 genetic test. There are no fields to fill out and return.
PXE International form
- Clinical Data Form and Consent to Release information: The Clinical Data Form gives PXE International information about the signs and symptoms of PXE that you experience. This is important as we are constantly researching the symptoms of PXE and their link to genetics. This form is not required to perform genetic testing, but it is appreciated. You may also consent to release your GeneDx genetic test results to PXE International on the Clinical Data Form. Access the Clinical Data Form at the link above or from the GeneDx website.
2. 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.
3. Submit the sample and the forms:
- To GeneDx: Send the completed Test Requisition/Sample Submission Form and the Clinical Data Form to the GeneDx laboratory with your sample. If required by your state, complete and return GeneDx's Informed Consent Form with the rest of the forms.
- To PXE International: Send the completed Clinical Data Form to PXE International. When you click Submit in the form, your email will open with the completed form attached. If not, please email completed Clinical Data Form to Abbie Moore.
4. Testing and results: 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 he or she will report the results back to you. You can ask your doctor for a copy of the report. If you consented to send PXE International your information, we will also receive a copy of the report. You can also make an appointment with our board certified genetic counselor to discuss your results. There is no charge for this appointment.
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To make an appointment with PXE International's board certified genetic counselor, please call 202.362.9599. Leave your name, address, email and phone number. Tell us whether you prefer daytime or evening. Our genetic counselor will get back to you within three business days. There is no charge for this appointment.
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1 Shi Y, Terry SF, Terry PF, Bercovitch LG, Gerard GF. Development of a rapid, reliable genetic test for pseudoxanthoma elasticum. J Mol Diagn. 2007 Feb;9(1):105-12.