The cause of an eye disorder called enhanced S-cone syndrome (ESCS) has been discovered. Affected individuals are sensitive to blue light and develop night blindness at an early age. A research team led by Val C. Sheffield, a Howard Hughes investigator at the University of Iowa College of Medicine, discovered that 94% of DNA samples from ESCS-affected individuals showed mutations in NR2E3, a photoreceptor gene that is also known as PNR (photoreceptor- specific nuclear receptor). Their work is published in the February issue of Nature Genetics.
Sheffield's lab, which focuses on identifying genes that cause human hereditary diseases--especially hereditary blindness-- discovered the ESCS mutations while studying another retinal disorder called Bardet Biedl syndrome (BB). However, they could not find any PNR mutations in patients with BB. They did, however, think PNR a good candidate for other eye diseases, so they screened nearly 400 DNA samples from people with other eye disorders, and found two samples that possibly contained a PNR mutation. Both patients suffered from ESCS.
To increase their sample size, they tested 35 ESCS-affected individuals from 29 families, obtaining samples from collaborators. "Lo and behold we found that nearly every sample had a mutation," remarks Sheffield. The research team also found that expression of NR2E3 is specific to the nuclear layer of the retina, which is lined by the nuclei of photoreceptors.
Humans have two types of photoreceptors, called rods and cones. Rods mediate black and white vision and are useful mainly at night. During the day, however, humans depend on cones for color vision. Cones come in three types--red, green, and blue--that are sensitive to different wavelengths of light. Discovering the molecular signals that determine why one cell becomes a rod or a cone, and how cone cells become blue-, green-, or red-sensitive are important questions in the study of eye development.
One hypothesis is that cone cells become blue by default unless they receive a signal to become red or green. Another hypothesis is that NR2E3 mutations alter a photoreceptor's fate, causing cells that would normally develop as rods to become cones instead.
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