People with achromatopsia, an inherited eye disorder, see the world literally in black and white. Worse yet, their extreme sensitivity to light makes them nearly blind in bright sunlight. Now, researchers at University of California, San Diego School of Medicine and Shiley Eye Institute at UC San Diego Health System have identified a previously unknown gene mutation that underlies this disorder.

"There are whole families with this sort of vision problem all over the world," said Jonathan Lin, MD, PhD, senior study author and an associate professor in the UC San Diego School of Medicine Department of Pathology. "We're very excited to have discovered a mutation in the ATF6 gene which plays a major role in this disorder."

Five other genetic mutations have previously been identified by research groups as pivotal in achromatopsia, which causes markedly reduced visual acuity and very poor or no color vision. "But we still had families that didn't have any of those gene mutations," said Lin, also a researcher at the UC San Diego Shiley Eye Institute. "We knew this meant there must be other genes and proteins involved."

The study, which involved an international collaboration of inherited retinal disease specialists, found that a mutation in the ATF6 gene damaged proteins necessary for proper function of the eye's cone photoreceptors. The eye has millions of these receptors, which control color recognition and daytime vision.

In achromatopsia, malfunction of the cone photoreceptors causes sufferers to be either totally or predominantly colorblind. This type of colorblindness is different from the more common version, which makes some people unable to distinguish between red and green. "Achromatopsia sufferers see images on the gray scale," explained Lin.

In the study, the scientists looked at 18 achromatopsia patients from 10 different families who had been identified as lacking the five previously known gene mutations. The families received testing in the lab of Susanne Kohl, PhD, the study's first author from Centre for Ophthalmology at University of Tuebingen in Germany. Kohl is a prominent researcher in the field, whose lab previously identified several of the achromatopsia gene mutations. Blood drawn from study subjects was analyzed using gene sequencing technology. All 18 were found to have the ATF6 gene mutation.

Lin said the ATF6 gene, when working properly, is a key regulator of the unfolded protein response (UPR), a cellular stress relief mechanism drawing major scientific interest due to its role in many diseases. The UPR is a critical player in helping the body's cellular proteins work correctly, which is extremely important since proteins carry out many biological functions. The UPR steps in and fixes misshapen or badly folded proteins, which can accumulate in the cell's endoplasmic reticulum if the cell becomes too stressed. If not fixed, the misshapen proteins won't work properly or they die.