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Typical best vitelliform dystrophy secondary to biallelic variants in BEST1

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. Green open access

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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.

Type: Article
Title: Typical best vitelliform dystrophy secondary to biallelic variants in BEST1
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/13816810.2023.2188227
Publisher version: https://doi.org/10.1080/13816810.2023.2188227
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: BEST1, EOG, ERG, autosomal recessive bestrophinopathy, best vitelliform macular dystrophy, bestrophin-1
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.ucl.ac.uk/id/eprint/10167009
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