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Kohl, S.* ; Zobor, D.* ; Chiang, W.C.* ; Weisschuh, N.* ; Staller, J.* ; Menendez, I.G.* ; Chang, S.* ; Beck, S.C.* ; Garrido, M.G.* ; Sothilingam, V.* ; Seeliger, M.W.* ; Stanzial, F.* ; Benedicenti, F.* ; Inzana, F.* ; Héon, E.* ; Vincent, A.* ; Beis, J.* ; Strom, T.M. ; Rudolph, G.* ; Roosing, S.* ; Hollander, A.I.* ; Cremers, F.P.* ; Lopez, I.* ; Ren, H.* ; Moore, A.T.* ; Webster, A.R.* ; Michaelides, M.* ; Koenekoop, R.K.* ; Zrenner, E.* ; Kaufman, R.J.* ; Tsang, S.H.* ; Wissinger, B.* ; Lin, J.H.*

Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia.

Nat. Genet. 47, 757-765 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Achromatopsia (ACHM) is an autosomal recessive disorder characterized by color blindness, photophobia, nystagmus and severely reduced visual acuity. Using homozygosity mapping and whole-exome and candidate gene sequencing, we identified ten families carrying six homozygous and two compound-heterozygous mutations in the ATF6 gene (encoding activating transcription factor 6A), a key regulator of the unfolded protein response (UPR) and cellular endoplasmic reticulum (ER) homeostasis. Patients had evidence of foveal hypoplasia and disruption of the cone photoreceptor layer. The ACHM-associated ATF6 mutations attenuate ATF6 transcriptional activity in response to ER stress. Atf6(-/-) mice have normal retinal morphology and function at a young age but develop rod and cone dysfunction with increasing age. This new ACHM-related gene suggests a crucial and unexpected role for ATF6A in human foveal development and cone function and adds to the list of genes that, despite ubiquitous expression, when mutated can result in an isolated retinal photoreceptor phenotype.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Endoplasmic-reticulum Stress; Optical Coherence Tomography; Transcription Factor; Retinal Structure; Alpha-subunit; Gene-therapy; Mouse Model; Congenital Achromatopsia; Total Colourblindness; Long-term
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 47, Issue: 7, Pages: 757-765 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)