PMID- 31900015
OWN - NLM
STAT- MEDLINE
DCOM- 20200804
LR  - 20200804
IS  - 1744-5094 (Electronic)
IS  - 1381-6810 (Linking)
VI  - 40
IP  - 6
DP  - 2019 Dec
TI  - Macular maldevelopment in ATF6-mediated retinal dysfunction.
PG  - 564-569
LID - 10.1080/13816810.2019.1706749 [doi]
AB  - 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.
FAU - Ritter, Markus
AU  - Ritter M
AUID- ORCID: 0000-0003-1406-8340
AD  - Moorfields Eye Hospital, London, UK.
AD  - Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
FAU - Arno, Gavin
AU  - Arno G
AD  - UCL Institute of Ophthalmology, University College London, London, UK.
FAU - Ba-Abbad, Rola
AU  - Ba-Abbad R
AD  - Moorfields Eye Hospital, London, UK.
AD  - UCL Institute of Ophthalmology, University College London, London, UK.
FAU - Holder, Graham E
AU  - Holder GE
AD  - Moorfields Eye Hospital, London, UK.
AD  - UCL Institute of Ophthalmology, University College London, London, UK.
AD  - National University of Singapore, Department of Ophthalmology, National 
      University Hospital, Singapore.
FAU - Webster, Andrew R
AU  - Webster AR
AUID- ORCID: 0000-0001-6915-9560
AD  - Moorfields Eye Hospital, London, UK.
AD  - UCL Institute of Ophthalmology, University College London, London, UK.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200103
PL  - England
TA  - Ophthalmic Genet
JT  - Ophthalmic genetics
JID - 9436057
RN  - 0 (ATF6 protein, human)
RN  - 0 (Activating Transcription Factor 6)
RN  - Foveal Hypoplasia, Isolated
SB  - IM
MH  - Activating Transcription Factor 6/*genetics
MH  - Adult
MH  - Color Vision Defects/*complications
MH  - Eye Diseases, Hereditary/etiology/genetics/*pathology
MH  - Female
MH  - Fovea Centralis/*abnormalities/pathology
MH  - *Homozygote
MH  - Humans
MH  - Macula Lutea/abnormalities/metabolism/*pathology
MH  - *Mutation
MH  - Nystagmus, Congenital/etiology/genetics/*pathology
MH  - Prognosis
MH  - Retina/*physiopathology
OTO - NOTNLM
OT  - ATF6
OT  - Achromatopsia
OT  - macular maldevelopment
EDAT- 2020/01/05 06:00
MHDA- 2020/08/05 06:00
CRDT- 2020/01/05 06:00
PHST- 2020/01/05 06:00 [pubmed]
PHST- 2020/08/05 06:00 [medline]
PHST- 2020/01/05 06:00 [entrez]
AID - 10.1080/13816810.2019.1706749 [doi]
PST - ppublish
SO  - Ophthalmic Genet. 2019 Dec;40(6):564-569. doi: 10.1080/13816810.2019.1706749. 
      Epub 2020 Jan 3.