A New Genetic Test Expands the Search for Disease-Causing Gene Mutations

December 08, 2014

When a person is diagnosed with an inherited retinal condition, identifying his or her disease-causing gene mutation can often be beneficial. It enables a physician to make a definitive diagnosis and determine which family members may be at risk for the condition. Also, identification of the mutation is necessary for participation in clinical trials of emerging gene therapies. However, more than 200 genes have been linked to retinal diseases, which often makes the search difficult.

A genetic-testing system offered by the Ocular Genetics Institute (OGI) at the Massachusetts Eye and Ear Infirmary (MEEI) is enabling researchers to cast a wide net for identifying mutations causing a patient’s inherited retinal disease. Known as the genetic eye disease (GEDi) test, the technology can pinpoint mutations in a vast majority of the genes known to cause retinal conditions. The system can also find mutations associated with early-onset glaucoma and inherited optic-nerve diseases. The GEDi test has received certification from the Clinical Laboratory Improvement Amendments (CLIA) program indicating that it has met quality standards necessary for commercial use. Research for the development of the system was funded in part by the Foundation Fighting Blindness. MEEI recently reported results of its GEDi studies in the journal Genetics in Medicine.

Genetic mutations are like misspellings in the code that’s responsible for determining many of a person’s traits, as well as his or her health and well-being. Many of these misspellings have no discernible effect. Others can lead to diseases including inherited retinal diseases, which cause vision loss and blindness. 

GEDi testing is now available through the OGI. Eric Pierce, M.D., Ph.D., the director of the Foundation’s Berman-Gund Laboratory for the Study of Retinal Degenerations, is also the OGI’s director.

 “We are very pleased with the results of our studies, which show that the GEDi test is both highly accurate and reproducible,” says Dr. Pierce. “Based on these results, we think the GEDi test and other panel-based tests are often the best approach for genetic diagnostic testing for patients with inherited retinal degenerations.” 

Panel-based tests target genes and mutations that are already known to cause disease. The GEDi was 98 percent accurate and results were highly reproducible for multiple test runs.

In contrast, a testing approach called whole exome sequencing (WES) searches all the coding region of a person’s entire set of genes. WES was only 88 percent accurate according to GEDi developers and is more costly than panel-based testing. Another drawback for WES is the large amount of generated data that may not be relevant to retinal diseases. However, WES can be a good approach to identifying disease-causing genes that have not yet been linked to the retina.

“Genetic testing is essential for patients and families wanting to better understand their eye disease and participate in clinical trials of emerging therapies,” says Stephen Rose, Ph.D., chief research officer at the Foundation. “The GEDi test is well positioned to play an important role in getting patients the genetic information they need to get on the right path to saving their vision.”

Patients and families affected by inherited retinal degenerations interested in genetic testing can visit the Foundation’s Web site to learn more about the process and the testing centers located in the United States and Europe.