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