de Guimaraes, Thales AC;
Lai, Francesco;
Colombatti, Raffaella;
Sato, Giovanni;
Rizzo, Roberta;
Kalitzeos, Angelos;
Michaelides, Michel;
(2024)
Structural and functional characterization of an individual with the M285R KCNV2 hypomorphic allele.
Ophthalmic Genetics
pp. 1-10.
10.1080/13816810.2024.2324046.
(In press).
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Structural and functional characterization of an individual with the M285R KCNV2 hypomorphic allele.pdf - Accepted Version Download (14MB) | Preview |
Abstract
BACKGROUND: Disease-causing variants in the KCNV2 gene are associated with "cone dystrophy with supernormal rod responses," a rare autosomal recessive retinal dystrophy. There is no previous report of hypomorphic variants in the disease. MATERIAL AND METHODS: Medical history, genetic testing, ocular examination, high-resolution retinal imaging including adaptive optics scanning light ophthalmoscopy (AOSLO), and functional assessments. RESULTS: A 16-year-old male with mild cone-rod dystrophy presented with reduced central vision and photophobia. Genetic testing showed two variants in KCNV2, c.614_617dupAGCG (p.207AlafsTer166) and c.854T>G (p.Met285Arg), the latter which was previously considered benign. Electrophysiological assessment revealed the pathognomic electroretinogram waveforms associated with KCNV2-retinopathy. Optical coherence tomography showed discrete focal ellipsoid zone disruption, while fundus autofluorescence was normal. Non-waveguiding cones corresponding to areas of loss of photoreceptor integrity were visible on adaptive optics scanning light ophthalmoscopy. Retinal sensitivity and fixation were relatively preserved, with a demonstrable deterioration after 14 months of follow-up. CONCLUSIONS: We provide functional and structural evidence that the variant M285R is disease-causing if associated with a loss-of-function variant. To the best of our knowledge, this is the first hypomorphic allele reported in KCNV2.
| Type: | Article |
|---|---|
| Title: | Structural and functional characterization of an individual with the M285R KCNV2 hypomorphic allele |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1080/13816810.2024.2324046 |
| Publisher version: | http://dx.doi.org/10.1080/13816810.2024.2324046 |
| Language: | English |
| Additional information: | © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | adaptive optics, AOSLO, cone dystrophy, cone-rod dystrophy, hypomorphic, inherited, KCNV2, microperimetry, VFMA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10189811 |
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