Casalino, G;
Khan, KN;
Armengol, M;
Wright, G;
Pontikos, N;
Georgiou, M;
Webster, AR;
... Michaelides, M; + view all
(2020)
Autosomal recessive bestrophinopathy: clinical features, natural history and genetic findings in preparation for clinical trials.
Ophthalmology
10.1016/j.ophtha.2020.10.006.
(In press).
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Abstract
Purpose: To investigate the clinical course, genetic findings and the phenotypic spectrum of autosomal recessive bestrophinopathy (ARB) in a large cohort of children and adults. / Design: Retrospective case series. / Participants: Patients with a detailed clinical phenotype consistent with ARB and/or biallelic likely disease-causing sequence variants in the BEST1 gene, identified at a single tertiary referral center. / Methods: Review of case notes, retinal imaging (color fundus photography, fundus autofluorescence [FAF], optical coherence tomography [OCT]), electrophysiologic assessment, and molecular genetic testing. / Main Outcome Measures: Visual acuity (VA), retinal imaging and electrophysiologic changes over time. / Results: 56 eyes of 28 unrelated patients were included. Compound heterozygous variants were detected in the majority of patients (19/27), with six alleles recurring in apparently unrelated individuals, the most common of which was c.422G>A, p.(Arg141His), (n = 4 patients). Mean presenting VA was 0.52 ± 0.36 LogMAR and final VA was 0.81 ± 0.75 LogMAR (p = 0.06). The mean rate of change in VA was 0.05 ± 0.13 LogMAR/year. A significant change in VA was detected in patients with a follow-up ≥ 5 years (n = 18) compared to patients with a follow-up ≤ 5 years (n = 10, p = 0.001). Presence of subretinal fluid and vitelliform material were early findings in the majority of subjects and this did not substantially change over time. A reduction in central retinal thickness was detected in the majority of eyes (80.4%) over the course of follow-up. Many subjects (10/26) showed evidence of generalised rod and cone system dysfunction. These patients were older (p < 0.001) and had worse VA (p = 0.02), than those with normal full-field electroretinography. / Conclusions: Although patients with ARB are presumed to have no functioning bestrophin channels, significant phenotypic heterogeneity is evident. The clinical course is characterized by a progressive loss of vision, with a slow rate of decline, providing a wide therapeutic window for anticipated future treatment strategies.
| Type: | Article |
|---|---|
| Title: | Autosomal recessive bestrophinopathy: clinical features, natural history and genetic findings in preparation for clinical trials |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ophtha.2020.10.006 |
| Publisher version: | https://doi.org/10.1016/j.ophtha.2020.10.006 |
| Language: | English |
| Additional information: | This is an Open Access article published under a Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | autosomal recessive bestrophinopathy, BEST1, retinal imaging, electrophysiology, genetics, and gene therapy |
| 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/10112149 |
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