Taylor & Francis Group
Browse
iopg_a_1706749_sm7419.xlsx (15.9 kB)

Macular maldevelopment in ATF6-mediated retinal dysfunction

Download (15.9 kB)
dataset
posted on 2020-01-04, 03:46 authored by Markus Ritter, Gavin Arno, Rola Ba-Abbad, Graham E. Holder, Andrew R. Webster

Background: Achromatopsia has been previously associated with mutations in the ATF6 gene. Rod-monochromatism, foveal hypoplasia, and disruption of the subfoveal photoreceptor layer are described as phenotypical features. We report detailed structural and electrophysiological assessment of two patients from two families, one manifesting severe macular maldevelopment and one with foveal hypoplasia.

Materials and methods: The patients underwent a complete ophthalmic examination including electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, and fundus photography. Genetic testing was performed by next-generation sequencing.

Results: In one patient, fundoscopy and SD-OCT revealed well-demarcated coloboma-like excavated lesions at the central macula of both eyes. Genetic analysis identified a novel homozygous p.Asp140Ter mutation in the ATF6 gene. The second patient had foveal hypoplasia in association with a homozygous ATF6 mutation affecting a splice donor site (c.1187 + 5G>C). In both patients, electrophysiological assessment showed normal rod-specific (DA 0.01) and dark-adapted bright white-flash ERGs (DA 10.0). 30 Hz flicker ERGs were undetectable. There were low-amplitude single-flash photopic ERGs (LA 3.0) with timing and shape suggesting S-cone origin.

Conclusions: The findings, particularly a case with severe macular maldevelopment, may expand on the phenotype previously associated with ATF6-mediated achromatopsia. In addition, the comprehensive electrophysiological assessment suggests that preserved S-cone activity can be detected in this particular molecular sub-type of cone dysfunction.

Funding

The work was supported by the NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology. Patient 1 underwent sequencing as part of the NIHR-Bioresource for Rare disease. The molecular analysis on patient 2 was undertaken from grants from the Moorfields Eye Charity. GA is supported by a Fight for Sight Early Career Investigator Award.

History

Usage metrics

    Ophthalmic Genetics

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC