ATF6 gene

Overview

Gene (OMIM No.)	ATF6 (#605537)
Function of gene/protein	Protein: Activating transcription factor 6 Transcription factor of the endoplasmic reticulum (ER) Activated upon ER stress resulting in recruitment of enzymes required to restore cellular homeostasis May play a crucial role in cone development
Clinical phenotype (OMIM phenotype no.)	Achromatopsia 7 (#616517)
Inheritance	Autosomal recessive
Ocular features	Nystagmus and photophobia from birth/early infancy Absent foveal reflex Variable central macular changes ranging from normal to well-demarcated atrophic areas
Visual function	Severely reduced visual acuity Poor/absent colour vision Bilateral central scotoma Rarely progresses
Systemic features	May be associated with sensorineural hearing loss
Key investigations	Full field ERG — Normal rod responses with severely reduced/absent cone responses FAF — Variable; parafoveal areas/rings of increased AF or a well-demarcated hypo-AF area corresponding to atrophy surrounded by a hyper-AF ring OCT — Foveal hypoplasia with absence of foveal ellipsoid zone or presence of a foveal hyporeflective zone
Molecular diagnosis	Next generation sequencing Targeted gene panels (retinal) Whole exome sequencing Whole genome sequencing
Management	Management of achromatopsia
Therapies under research	Oral glycerol phenylbutyrate (PBA) (NCT 04041232, early phase 1)
Further information	OMIM

Wu J, Rutkowski DT, Dubois M, et al. ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Dev Cell. 2007;13(3):351-364
Kohl S, Zobor D, Chiang WC, et al. Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia. Nat Genet. 2015;47(7):757-765
Ansar M, Santos-Cortez RL, Saqib MA, et al. Mutation of ATF6 causes autosomal recessive achromatopsia. Hum Genet. 2015;134(9):941-950.
Mastey RR, Georgiou M, Langlo CS, et al. Characterization of Retinal Structure in ATF6-Associated Achromatopsia. Invest Ophthalmol Vis Sci. 2019;60(7):2631-2640

Updated on February 7, 2021