Renowned geneticist, Stephen Daiger, Ph.D., makes the case for genetic testing
June 25, 2021
University of Texas geneticist and researcher, Stephen Daiger, Ph.D., tells us why he says everyone with an inherited retinal disease (IRD) should be offered genetic testing, how testing has advanced, and why identifying genetic mutations is key to the future of retinal research.
Stephen Daiger, Ph.D., Sara Bowne, Ph.D., and Lori Sullivan, Ph.D. work together in the Laboratory for Molecular Diagnosis of Inherited Eye Diseases at the University of Texas in Houston (UTHealth) to find genes and mutations causing retinitis pigmentosa and related conditions.
Keeping up with the rapidly evolving science surrounding IRDs is a full-time job. That’s why we reached out to Stephen Daiger, Ph.D. He is the Director of the Laboratory for Molecular Diagnosis of Inherited Eye Diseases at the University of Texas at Houston. His research, spanning decades, focuses on the genes and mutations that cause IRDs. He talks with us about the ongoing identification of new mutations and why genetic testing has become such a key element for anyone living with inherited vision loss.
Q: Before we talk specifically about genetic testing, would you first tell us how our understanding of the genetics of inherited retinal diseases (IRDs) has changed over the years?
A: When we first started working on the genetic causes of inherited retinal diseases (IRDs), in about 1985, we were looking for the “few” genes that contribute to the causes of these diseases. Eventually, there emerged extremely bad news for the many dozens of us around the world who worked on this problem—which, amazingly, later changed into extremely good news.
The bad news was we had discovered, by 2010, that there weren’t one or two genes but literally multiple hundreds of genes that can harbor a mutation or change which leads to retinitis pigmentosa, Stargardt disease, or many of the other conditions we call inherited retinal diseases. There was a despair that it was too complicated for us. What were we going to do?
Q: How did that somehow turn into good news?
A: Genetic testing is one reason. As recently as 15 years ago, it was only possible to find the cause of inherited retinal disease in about five to 10 percent of people. The state of the art in 2021, however, is that we can now find the cause of an IRD using advanced DNA technology in at least 60 to 70 percent of people. That means if you give a blood or saliva sample to a healthcare professional and they send your sample to a testing laboratory, the lab will run genetic testing and then—for most people—report back, “This is the exact, specific cause of your vision loss.”
But more so, and the thing we never reckoned with in those early days, (at least speaking for myself), is how this would open the door to many new possibilities. Biotech companies basically looked across the entire panel of known causes and said, “Well, we have a product in the pipeline that could actually solve this particular problem. Let’s develop it.” That opened the flood gates to natural history studies and many new, potential treatments.
Stephen Daiger, Ph.D., talks about the importance of genetic testing at a 2018 VisionWalk fundraiser.
Q: Are you talking about clinical trials?
A: Yes. In my opinion, and I’m certainly not alone in this, everyone in the U.S., frankly, in the world, who has an inherited retinal disease in their family should, when they can, get genetic testing to find out the cause of their disease. That’s the absolute bedrock, baseline information that a patient needs to, today, enroll in a clinical trial.
Q: What is the most important thing for people to know about genetic testing for ophthalmology problems?
A: The process starts with the ophthalmologist, but it should quickly lead to connection with a genetic counselor. Families can also get involved more directly with Spark’s ID YOUR IRD® or the My Retina Tracker® program and registry from the Foundation Fighting Blindness. Both programs offer no-cost, genetic testing to those who qualify.
Q: Sending someone’s DNA off for genetic testing is a pretty straightforward process, isn’t it?
A: On the patient’s side, yes. First a DNA sample is taken from the patient—blood, saliva or cheek swab—and sent to the appropriate testing facility. When the results come back, the clinician or the genetic counselor makes sense of those results and explains the findings to the patient. A genetic counselor is utterly, absolutely essential to this whole situation because they can read the technical reports. They can talk to the clinician about the eye findings and then they can work with the families. As you can probably tell, I sort of have a sense of worship towards genetic counselors because what they do is brilliant.
Q: Why do some tests come back “negative” or “inconclusive”?
A: Inconclusive could mean one of two things: Either we think we found it, but we’re not sure—that’s certainly inconclusive; or… we have no clue; we couldn’t find it. That’s when a gene for a mutation hasn’t been identified and it’s not part of the current testing panels.
That, “We don’t have a clue; we couldn’t find it,” answer is now running around 20 percent of results. In fact, we have a large consortium involving the Foundation Fighting Blindness, Harvard, UC San Diego, and UT Houston working to define what we call the “elusive remaining genes.” We want to figure out that remaining 20 percent.
Q: If our understanding of the genetic causes of IRDs is constantly evolving, what is the key to making sure you’re getting the best and most up-to-date information and care?
A: The patients and families we’ve worked with through the years, the ones that have done the best, first of all, have an ophthalmology or genetic or university clinic they go to on a regular basis. They get in touch once a year and say, “Hey doc, I haven’t heard from you in a while. Where are we with this?” Patients and their families have to become their own advocates.
Everyone in the U.S., frankly, in the world, who has an inherited retinal disease in their family should, when they can, get genetic testing to find out the cause of their disease.”
Q: What kind of genetic test should people with an IRD discuss with their eye care specialist?
A: There are companies that will now do clinically certified whole-exome testing. A couple of companies will even do whole-genome testing. Those may be the methods of choice in the long run, but there are technical reasons why they’re not as effective today. I think the simplest reason is this: It is cleaner to look at a test with a panel of the 300 genes known to be associated with IRDs, than to look at 25,000 genes all at the same time.
Genetic testing companies use a technique called targeted capture, where they literally use little probes to physically capture from the patient’s DNA sample a couple hundred—typically 300 to 350—of the known causes of these diseases. And I can tell you, every company that we have been associated with who does panel testing, assesses their panel about every six months and says, “Oh my goodness. We found there are three more genes identified. We’ve got to start the process of adding them to the panel.”
Q: If the genetic testing panels are becoming more complete with every scientific advancement, what has that done to the cost of these tests?
A: The cost of the first human DNA sequencing was probably—nobody knows for certain—but let’s say a hundred million dollars. Now, the cost of full-genome sequencing is hovering around a thousand dollars, and the cost of panel testing, which is partly born by companies, is hovering around $500—and sometimes costs nothing at all.
At Eye Want 2 Know, we believe the time to test is now. If you would like to know more about no-cost, IRD panel testing, check out the ID YOUR IRD and the My Retina Tracker programs, which offer no-cost genetic testing and genetic counseling, and then discuss the possibility of ordering a genetic test with your eye care specialist.
Stephen P. Daiger, Ph.D.
Stephen P. Daiger, Ph.D., is the Director of the Laboratory for Molecular Diagnosis of Inherited Eye Diseases at the University of Texas in Houston (UTHealth). His research focuses on the genes and mutations causing inherited retinal diseases such as retinitis pigmentosa, Leber congenital amaurosis, and macular degeneration.