Research Fact Sheet ~ Genetic Testing
Background
With advances in genetic science, we now know that there are over 200 genes associated with retinal degenerative diseases. Mutations (errors) in these genes compromise the vision of people with Leber congenital amaurosis, retinitis pigmentosa, Stargardt macular dystrophy and other similar conditions. Two patients who seem to have the same eye condition may have mutations in different genes. The location of these mutations can now be identified by a variety of sophisticated genetic techniques.
Each gene is made up of DNA, which has hundreds of subunits called base pairs. Mutations can occur anywhere in this string of base pairs, so even when two people have vision loss due to an error in the same gene, they may have completely unique mutations.
To learn more about genetics visit http://ghr.nlm.nih.gov/handbook.
What is genetic testing?
Genetic testing is more formally called Molecular Genetic Testing or genotyping. It is usually done as part of genetic counselling. It involves taking a sample of your DNA (usually a blood sample) and examining it in a laboratory.
Genetic testing can give you and your doctor more information about your condition if mutation(s) are identified; however, testing does not always give a clear result. Although there have been remarkable advances in this field over the past 10 years, many of the genes associated with vision loss remain unidentified.
Why is genetic testing done?
Successful genetic testing can add to the information people receive from genetic counselling. Even without such tests, a counsellor can tell you a lot about your condition by reviewing records from your ophthalmologist and asking you questions about your vision and family. She/he can tell you how your condition may develop and the risk of vision loss for other members of your family. Adding genetic testing to counselling may:
- Confirm your diagnosis
- Tell you more about your prognosis
- Determine your eligibility for some emerging therapies
Most people who contact the FFB asking about genetic testing do so because they are interested in a clinical trial of an emerging therapy. There are many approaches to vision research now under way, therapies based on specific genetic mutations are only one approach. When a therapy is developed for a specific genetic subtype, ONLY people with that specific genetic mutation will be eligible to participate in the trial, or able to benefit from the therapy, if it is approved.
The FFB is working to develop a patient registry that will help connect people to clinical trials appropriate for their condition. Learn more.
Will genetic testing identify my mutation?
The likelihood of receiving an answer from genetic testing varies with your condition. Some conditions are associated with only a small number of genes and the genes are well known. In other cases, there are many possible mutations in many different genes – and testing will be more difficult. In general, people with x-linked retinoschisis or choroideremia are most likely to get a result, people with Leber congenital amaurosis or Stargardt macular dystrophy are next, while retinitis pigmentosa (RP) is likely to be more challenging, particularly for those with recessive RP. Your genetic counsellor can provide you with an estimate of success specific to you. He/she can also identify the most appropriate laboratories to test your sample based on your condition and family history.
How can I arrange to have genetic testing?
A genetic counsellor can work with you to arrange testing. Unfortunately, this is still difficult in many parts of the country, where genetic counselling for eye conditions is not widely available and genetic tests even less so. However many large Canadian cities have a retinal dystrophy clinic or a test centre with a genetic counsellor.
Ask your ophthalmologist to refer you to the clinical genetics service in your area. The Canadian Association of Genetic Counsellors offers a listing of these clinics at http://cagc-accg.ca (click on Genetic Clinics). Genetic counsellors in Canada have access to many professional resources to keep them updated about the latest possibilities for genetic testing and to identify international labs testing for specific genes.
What information needs to be in the referral from my doctor?
- Name
- Address and phone number
- Present diagnosis
- Information about other family members with vision problems
- Details of first symptoms and the age at which they started
- The results of tests such as ERG, VEP, OCT, visual fields & visual acuity tests
If sufficient testing information is not available from your own doctor you may have to be referred to a retinal specialist for further testing before genetic counselling can begin.
How long will it take?
After a sample has been submitted for molecular genetic testing, it will likely take months - and sometimes more than a year – to receive a result. Even Canada’s largest centres will likely be sending your sample out to one or more international laboratories for testing. Ask your genetic counsellor how you will be informed about the results when they do arrive.
If your mutation is not identified, it may be possible for your DNA specimen to be stored and retested again as more genes are identified. Ask your genetic counsellor about the possibilities for holding and retesting your specimen and the length of time the specimen might be held.
Will my provincial health plan pay?
In some provinces, your genetic counsellor can complete an application for coverage of genetic testing. It may take months for such a claim to be processed and not all provinces have this option.
Can I pay for it myself? What will it cost?
Depending on the regulations in your province, you may be able to pay for testing yourself – in some cases this will be the only option. The cost will depend on your condition, the number of genes to be tested and the lab methods used.
With the support of the FFB and others, testing panels with some of the most common mutations for each condition have been developed. When this method can be used, testing will cost around $300. However, if your mutation is not a common one the result will be negative. These panels are constantly being updated, and are becoming faster and less costly.
Sequencing is a detailed analysis of all the known genes for a certain condition. It has a better chance of finding your mutation but is much more costly and time intensive. Sequencing often cost $2000 or more, but a positive result cannot be guaranteed, as your mutation may not be within the genes known to cause your condition.
Will the availability and efficacy of testing improve?
Yes, we anticipate that testing will improve in the next few years. With your support, Canadian scientists discover new vision loss genes each year; other scientists around the world are doing the same. The tools for performing these tests are continually being updated, and rapidly becoming more affordable. In the future, we anticipate that genetic testing will be able to identify most mutations and will become a more routine option for Canadians living with vision loss.
Updated October 14, 2011: Reviewed by Joanne Sutherland and Megan Day, Ocular Genetic Counsellors, Sick Children’s Hospital, Toronto, Dr. Robert Koenekoop, Scientist and Retinal Specialist, Montreal Children’s Hospital, and Dr. Jane Green, Ocular Genetics Research, Memorial University of Newfoundland, St. John’s.