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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 möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Nature Genetics
Quellenangaben Band: 47, Heft: 7, Seiten: 757-765 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)