Researchers at the University of California, San Diego School of Medicine and the Shiley Eye Institute at UC San Diego Health System have found a previously unidentified genetic mutation that plays a key role in the onset of an inherited eye disorder known as achromatopsia.
People with achromatopsia view the world as though they were watching an old black-and-white television set, and they have an extreme sensitivity to light that makes it nearly impossible to see in bright sunlight. The new mutation, published online Monday in the journal Nature Genetics, brings the total number of mutations discovered to six.
“There are whole families with this sort of vision problem all over the world,” Dr. Jonathan Lin, senior author of the study and an associate professor in the UC San Diego School of Medicine’s Department of Pathology, said. “We’re very excited to have discovered a mutation in the ATF6 gene which plays a major role in this disorder.”
New mutation affects a different process
Despite the fact that five genetic mutations had already been linked to achromatopsia, Dr. Lin said that there were still families that had the condition without any of those mutations, which led him to believe that there must be other genes involved. Sure enough, he and an international team of colleagues discovered a new mutation in the ATF6 gene that damaged proteins required for the eye’s cone photoreceptors to function properly.
The study authors looked at 18 achromatopsia patients from 10 different families, none of which possessed any of the five previously identified genetic mutations. Blood samples provided by the participants were analyzed using gene-sequencing technology, and each of the 18 participants were found to possess the newly-discovered ATF6 gene mutation.
When working correctly, the ATF6 gene is a key regulator of the unfolded protein response or UPR, a cellular stress relief mechanism drawing major scientific interest due to its role in many diseases, Dr. Lin explained. The UPR process helps the body ensure that its cellular proteins are functioning correctly, fixing badly folded or misshapen proteins to keep them from dying off.
“In this particular disease, we think a mutation in the ATF6 gene disrupts the UPR process and causes the production of bad proteins which keep cone photoreceptors from functioning properly,” he explained, adding that the UPR is a different molecular mechanism than those that the other five gene mutations affect. Dr. Lin added that his team was “really excited” because UPR represents “a new pathway found to be involved in this disease.”