Duke University team discovers a gene mutation tied to severe myopia

CorrespondentJune 16, 2013 

When it comes to reading, teachers re-tell the same stories year after year. One student holds a book inches from his face and requests to sit in the front row. His sister seems perfectly content in a desk toward the back of class and can easily read papers at arm’s length.

It’s not uncommon for children to have varying degrees of eyesight. But is such a big difference normal among siblings?

The reasons why one child inherits a parent’s nearsightedness while another offspring has perfect vision have long been fuzzy. Now, new research out of Duke University is bringing some clarity to this puzzle.

Known clinically as myopia – and frequently blamed on significant time spent reading – nearsightedness is the most common eye disease affecting humans. Nearly 30 percent of American adults have myopia, according to the American Optometric Association. The condition occurs when the eye is either oval-shaped (rather than round) or the cornea – the transparent covering over the front of the eye – is too curved. In either case, the eye is unable to properly focus the light coming through the pupil.

The result is blurry vision, meaning a nearsighted person must stand closer to an object that a normal-sighted person in order to see it clearly. For example, a nearsighted person must stand 20 feet away from a street sign to see it as well as a normal-sighted person can at 40 feet.

But, according to research published in the American Journal of Human Genetics, the genetic cause behind myopia could now be a little clearer. Duke researchers found that a newly-identified genetic mutation that affects copper metabolism and oxygen regulation in eye tissue is a culprit in cases of severe myopia.

High-grade myopia is inherited and occurs most commonly in Asian cultures. But it also affects nearly 2 percent of nearsighted Americans, increasing their risks for additional eye problems, such as detached retinas, cataracts and glaucoma.

Several myopia-associated genes have already been discovered, but this one – SCO2 – is particularly important in the study of high-grade disease, said Terri Young, M.D., an ophthalmology, pediatrics, and medicine professor at Duke. When functioning properly, SCO2 helps metabolize copper, an element vital to controlling oxygen levels in eye tissue. A malfunctioning gene can allow oxygen levels to rise too high, increasing stress on the tissue. These high levels can, ultimately, alter the eye’s development and function, she said.

“This is the first time a gene mutation like this has been discovered,” she said. “It’s one found in cases of inherited severe myopia among Caucasians where only one parent carries the gene for the condition and where the nearsightedness isn’t associated with any other health conditions.”

Finding the mutation

To find genetic mutations common among individuals with high-grade myopia, Young and her colleagues within Duke’s Eye Center, Center for Human Genetics, and graduate medical school in Singapore analyzed DNA extracted from the blood and saliva of four individuals all from the same 11-member American family of European ancestry.

Her team used a new sequencing method – next-generation sequencing (NGS) – to produce large, more precise quantities of data. NGS enables researchers to sequence larger numbers of DNA pairs faster than when using the more traditional method, electrophoresis.

“Using next-generation sequencing, we were able to obtain more than 50 times the number of DNA copies than we would have through traditional sequencing,” she said. “It was because we had more copies that we knew what we were seeing with the mutation was real. That’s how we found the gene and discovered that the mutation was only present in people with myopia.”

The team also found three additional SCO2 genes mutations in an additional 140 people.

After identifying the SCO2 gene mutation in human eye tissue, researchers explored the gene’s expression in mice to further confirm their findings. They induced nearsightedness in otherwise normal-sighted, newborn mice by putting a translucent contact lens over one eye in each animal. After six weeks, they analyzed the eye tissue to see where SCO2 was most expressed, and in this case, mutated. By attaching a stain to the gene, they found these genes were most expressed in the retina – the tissue where the eye actually sees images – and the white, protective part of the eye called the sclera.

Combining the results from both human and mouse eye tissue analysis highlights the existing connection between low levels of copper in the body and eye disease, she said.

“What we’ve found – and what’s in pre-existing research – suggests that copper deficiencies could set people up to become nearsighted,” Young said. “We didn’t specifically test diets, but it’s possible that mineral- and vitamin-deficient diets could play a role.”

If that’s the case, she said, taking copper supplements could conceivably slow down or stop myopia’s development.

What’s next?

Even though malfunctioning SCO2 has a significant, negative impact on eyesight, it is likely a very rare mutation, Young said. So, rather than test for it alone, her group plans to add it to a panel of studies known myopia-associated genes.

Additional work is also ongoing, exploring the impact an SCO2 mutation could have outside of eye disease. According to Dennis J. Thiele, Ph.D., a pharmacology and cancer biology professor at Duke who wasn’t part of Young’s team, one of the SCO2 mutations is pivotal in a deadly form of cardiomyopathy, a condition that causes the heart muscle to weaken and eventually leads to heart failure.

Because this gene mutation can affect multiple body systems, it’s important for investigators to continue their explorations, said Gary Heiting, a practicing ophthalmologist in Minnesota, as well as the editor of All About Vision, an online eye-education publication. Knowing more about SCO2 will help scientists and doctors better understand how much of eye health is inherited and how much is cause by day-to-day activities.

“This new research is an important step in understanding what causes myopia to develop in some children and not others. But, it is just one step,” Heiting said. “Further research, including research in the areas of genetics, nutrition, reading behaviors, time spent indoors versus outdoors during childhood, and other factors, is needed before we will fully understand what causes myopia and what we can do to effectively reduce the incidence and prevalence of nearsightedness in the future.”

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