Genetic Testing Helps Physicians Zero In On Eye Disease

In the September issue of Investigative Ophthalmology & VisualScience (IOVS), scientists at the U-M Department of Ophthalmology andVisual Sciences report on the arRP-I sequencing array, the firsttechnology to screen simultaneously for mutations in multiple genes ona single platform.

This is a novel tool for scientists and physicians alike, says leadauthor and Kellogg scientist Radha Ayyagari, Ph.D. "For diseases thatare associated with multiple genes, like RP, we now have a new andfaster method for identifying the underlying genetic basis. This isalso useful in analyzing complex patterns of inheritance and forunderstanding how causative genes might interact with each other."

RP is a group of diseases, affecting one in every 3,500 individuals, inwhich retinal degeneration leads to blindness or severe vision loss.

Among the outward signs and symptoms are loss of peripheral vision,night blindness, and abnormal results from an electroretinogram (ERG),a test that measures the electrical activity and function of theretina. A patient with the autosomal recessive form of the disease(arRP) has inherited one gene from each parent, neither of whom isaffected by RP.

It is nearly impossible to identify which form of the disease a patienthas through a clinical examination alone, notes John R. Heckenlively,M.D., a specialist in inherited eye disease who also participated inthe study.

"Identifying the precise genetic mutation responsible for anindividual's disease will allow us to provide a precise diagnosis, andthis knowledge will also allow us to apply genetic therapies as theyare developed," he says.

Some clues to treatments are beginning to emerge in animalmodels, and scientists expect future therapies to be very specific tothe type of RP.

"Perhaps one patient will benefit from dramatically limiting exposureto sun or artificial light, and another will use certain vitamins orsupplements to stop progression of the disease," says Heckenlively."Obtaining a molecular diagnosis is going to be very important inhelping to guide gene-based treatments for patients in the comingyears," he concludes.

Ayyagari's study involved 70 individuals with a clinical diagnosis ofarRP. Thirty-five had not been previously screened, and 35 others withknown genetic mutations were screened to validate the results.

The arRP-I chip contained sequences, or genetic codes, of 11 genes thatcarry approximately 180 mutations associated with early-onset retinaldegenerations. To date more than 30 genes have been identified forvarious forms of RP. Ayyagari notes that while the size of the chipcurrently limits the ability to array all known RP genes, largerplatforms are likely to be available soon.

The arRP-I chips designed by the Kellogg research team produced 97.6percent of the sequence analyzed with greater than 99 percent accuracyand reproducibility. The material cost of the arRP-I chip was 2