New cause of colour blindness identified: gene mutation

The findings, which were published in Nature Genetics on 2 June, could lead to new, targeted treatments for that form of colour blindness.The researchers found that mutations to a gene called ATF6, a key regulator of the unfolded protein response, can lead to achromatopsia, a hereditary visual disorder characterised by colour blindness, decreased vision, light sensitivity, and uncontrolled eye movent in children.The unfolded protein response is a mechanism that cells use to prevent the dangerous accumulation of unfolded or misfolded proteins. Several drugs that activate that pathway have already been approved by the FDA [United States Food and Drug Administration] for other conditions and could potentially benefit patients with achromatopsia, Dr Stephen Tsang, MD, Institute of Human Nutrition, at Columbia University Medical Center, New York, said. Five genes had previously been linked to achromatopsia; however, they accounted for only about half of all cases, Dr Tsang said. Using next-generation gene sequencing on a small group of patients, we found that mutations in a sixth gene – ATF6 – can independently lead to the disease. The new mutations were initially identified by sequencing the exomes of three children with achromatopsia who receive care at New York Presbyterian Hospital. None of the children had mutations in the five known achromatopsia genes. ATF6 mutations were subsequently observed in 15 patients with achromatopsia from nine other families in the study. All of the patients were found to have significant fovea hypoplasia, a characteristic not commonly seen in other achromatopsia patients.By analysing skin cells from the patients with achromatopsia and their unaffected family mbers, the researchers confirmed that the ATF6 mutations were interfering with the signalling pathway that regulates the unfolded protein response. Surprisingly, the patients had no other ATF6-related abnormalities. ATF6 is found in every cell of the body, but for some reason only the cone cells were affected, Dr Tsang said.The researchers estimate that ATF6 mutations account for only about 1% of cases of the disease. As we sequence more and more patients with achromatopsia, we’re likely to identify other genes, Dr Tsang said. I think the important lesson of this study is that it donstrates how advanced technologies are bringing precision medicine to the field of ophthalmology. Certain diseases may look the same based on the clinical diagnosis, but we’re finding that each patient is a little bit different and may benefit from a personalised approach to treatment.

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