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Susanne Kohl; Exome sequencing identifies novel gene defect in achromatopsia. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
Achromatopsia (ACHM; rod monochromatism, total colorblindness) is an autosomal recessively inherited retinal disorder characterized by low vision, lack of color discrimination, photophobia and nystagmus. Electroretinographic recordings show absence or severely reduced cone photoreceptor function in these patients, while rod function is essentially normal. Until recently, mutations in five genes (GNAT2, PDE6C, PDE6H, CNGA3, CNGB3) encoding for functional components of the cone phototransduction cascade ([Opsin] – Transducin – Phosphodiesterase – Cyclic Nucleotide Gated (CNG) Channel) had been shown to be associated with this disorder. Now mutations in ATF6 were identified by whole exome sequencing in patients presenting with typical findings of ACHM. There was no evidence for extraocular symptoms. Which is surprising: in contrast to the other ACHM genes, ATF6 has no specific or exclusive function in phototransduction. It encodes the ubiquitously expressed Activating Transcription Factor 6 that is known for its function as a key regulator of the Unfolded Protein Response (UPR) and cellular endoplasmic reticulum (ER) homeostasis. These findings suggest an unexpected but important role of ATF6 for human cone photoreceptor development and function, and warrant further studies to understand why mutations in ATF6 result in selective loss of cone function.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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