Disease-Causing Gene Identified After Family's 20-Year Quest

One family's disease-causing gene is identified after a nearly 20-year quest.

ByKIM CAROLLO, ABC News Medical Unit
February 9, 2011, 9:12 AM

Feb. 10, 2011— -- It took almost 20 years, but Betti Lidsky finally found out what caused three of her four children to go blind.

Betti's two daughters and son, now in their 30s, were diagnosed with retinitis pigmentosa when they were teenagers in 1992. Retinitis pigmentosa, or RP, is a group of genetic conditions that lead to retinal degeneration and can cause severe, incurable vision problems in later adulthood. It can sometimes lead to blindness. Neither Betti nor her husband have RP, but both carried the recessive gene for it.

"It was initially very devastating," said Lidsky, who is from south Florida. "My husband cried for a year and a half."

Researchers have identified more than 50 genes associated with RP, but no one could figure out which gene caused the condition in the Lidsky children.

Finally, last spring, the family got the news they spent years hoping for: researchers at the University of Miami's John T. Macdonald Foundation Department of Human Genetics finally identified the gene responsible for RP in their family.

"It was huge news. It was monumental. For 18 years, we searched for the genetic cause," said Lidsky.

"They had their DNA tested for many candidate genes, but none of the known RP genes caused it in their family," said Margaret A. Pericak-Vance, associate dean for human genomic programs and director of the Hussman Institute for Human Genomics at the University of Miami.

Vance and her colleagues from the University of Miami, Mount Sinai School of Medicine in New York and Vanderbilt University in Nashville, Tenn. used a new DNA sequencing technique that enabled them to look at all possible variations in all genes. Older technology did not allow that kind of analysis.

"This has only been possible for the past year and a half," said Pericak-Vance. "Before, we couldn't do such a complete scan. We would have had to use multiple families to identify a gene."

Experts say the finding is very significant and can finally provide an answer after years of agonizing questions for the Lidsky family. They also say the finding could offer hope for someday finding a treatment for RP.

Retinitis Pigmentosa: Vision Problems Slowly Progress Into Late Adulthood

The gene identified by the University of Miami researchers accounts for about 15 percent of RP in families of Ashkenazi Jewish descent, like the Lidskys. But the disease is found in all ethnicities and races, and affects millions of people around the world.

"This is such a hugely variable condition that involves mutations in so many different genes that it affects individuals from all parts of the world and generally wouldn't be possible to affect one race or ethnicity more than another," said Dr. Abdhish R. Bhavsar, a retinal surgeon and clinical correspondent for the American College of Ophthalmology.

Among the first signs of RP are night blindness and tunnel vision.

"Patients have night blindness in adolescence and start losing vision in young adulthood, then start developing tunnel vision, and then start losing their vision after age 50," said Dr. Eliot Berson, professor of ophthalmology at Harvard Medical School and director of Harvard's Berman-Gund Laboratory at the Massachusetts Eye and Ear Infirmary in Boston.

Before they were diagnosed, Betti Lidsky's children had the telltale signs of night blindness and tunnel vision.

One of her daughters was in theater school and started falling off the stage because of tunnel vision. She also often crashed into things when walking.

"Some people with RP still have 20/20 vision but are virtually blind. They can read the eye chart, but their field of vision is so narrow can't find their way out of the room," said Berson.

Berson says RP is treatable. He was one of the authors of a study sponsored by the National Eye Institute that found it could slow the disease with vitamin A palmitate, given in a certain dose as part of a regimen that includes eating oily fish.

He stressed there's often confusion about vitamin A palmitate.

"It's not pure vitamin A, and it's not beta-carotene. Beta-carotene is not a suitable substitute for vitamin A palmitate, and pure vitamin A can be toxic in very high doses."

But Bhavsar says that study had some safety issues and the findings were never proven. As far as other potential treatments are concerned, there really isn't anything that works particularly well.

"There are some treatments that suggest some benefits, but at the present time, it would be most accurate to say there is no standard proven accepted treatment," he said.

Researchers are looking into other avenues, including gene therapy and implanting a growth factor that can slow retinal degeneration.

The discovery of the Lidsky family gene gives experts hope, but they know that a potential cure is way off.

Lidsky now has 11 grandchildren, and she and her affected children worry about how many of the next generation will have RP. Now that the family gene has been isolated, getting an answer will be much easier.

"Now, we can test them all with a simple blood test," she said.

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