eprintid: 10167009
rev_number: 12
eprint_status: archive
userid: 699
dir: disk0/10/16/70/09
datestamp: 2023-03-23 16:42:37
lastmod: 2024-03-21 13:58:30
status_changed: 2023-03-23 16:42:37
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Dhoble, Pankaja
creators_name: Robson, Anthony G
creators_name: Webster, Andrew R
creators_name: Michaelides, Michel
title: Typical best vitelliform dystrophy secondary to biallelic variants in BEST1
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D08
keywords: BEST1, EOG, ERG, autosomal recessive bestrophinopathy, best vitelliform macular dystrophy, bestrophin-1
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: BACKGROUND: Pathogenic variants in BEST1 can cause autosomal dominant or autosomal recessive dystrophy, typically associated with distinct retinal phenotypes. In heterozygous cases, the disorder is commonly characterized by yellow sub-macular lesions in the early stages, known as Best vitelliform macular dystrophy (BVMD). Biallelic variants usually cause a more severe phenotype including diffuse retinal pigment epithelial irregularity and widespread generalized progressive retinopathy, known as autosomal recessive bestrophinopathy (ARB). This study describes three cases with clinical changes consistent with BVMD, however, unusually associated with autosomal recessive inheritance. MATERIALS AND METHODS: Detailed ophthalmic workup included comprehensive ophthalmologic examination, multimodal retinal imaging, full-field and pattern electroretinography (ERG; PERG), and electrooculogram (EOG). Genetic analysis of probands and segregation testing and fundus examination of proband relatives was performed where possible. RESULTS: Three unrelated cases presented with a clinical phenotype typical for BVMD and were found to have biallelic disease-causing variants in BEST1. PERG P50 and ERG were normal in all cases. The EOG was subnormal (probands 1 and 3) or normal/borderline (proband 2). Probands 1 and 2 were homozygous for the BEST1 missense variant c.139C>T, p.Arg47Cys, while proband 3 was homozygous for a deletion, c.536_538delACA, p.Asn179del. The parents of proband 1 were phenotypically normal. Parents of proband 1 and 2 were heterozygous for the same missense variant. CONCLUSIONS: Individuals with biallelic variants in BEST1 can present with a phenotype indistinguishable from BVMD. The same clinical phenotype may not be evident in those harboring the same variants in the heterozygous state. This has implications for genetic counselling and prognosticationA.
date: 2024
date_type: published
publisher: Informa UK Limited
official_url: https://doi.org/10.1080/13816810.2023.2188227
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2011886
doi: 10.1080/13816810.2023.2188227
medium: Print-Electronic
lyricists_name: Michaelides, Michel
lyricists_name: Robson, Anthony
lyricists_id: MMICH14
lyricists_id: AROBS26
actors_name: Michaelides, Michel
actors_id: MMICH14
actors_role: owner
funding_acknowledgements: [Supported by a grant from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology]
full_text_status: public
publication: Ophthalmic Genetics
volume: 45
number: 1
pagerange: 38-43
event_location: England
citation:        Dhoble, Pankaja;    Robson, Anthony G;    Webster, Andrew R;    Michaelides, Michel;      (2024)    Typical best vitelliform dystrophy secondary to biallelic variants in BEST1.                   Ophthalmic Genetics , 45  (1)   pp. 38-43.    10.1080/13816810.2023.2188227 <https://doi.org/10.1080/13816810.2023.2188227>.       Green open access   
 
document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10167009/2/Michaelides_Final%20manuscript%20Re%20submission%20BEST1%2019.2.2023.pdf