{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:53:58Z","timestamp":1790704438429,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Science Research Program of the National Research Foundation of Korea (NRF)","award":["2019R1A2C2002393"],"award-info":[{"award-number":["2019R1A2C2002393"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Autosomal recessive bestrophinopathy (ARB) is a rare subtype of bestrophinopathy caused by biallelic mutations of the BEST1 gene. ARB is characterized by multifocal subretinal deposits accompanied by macular edema or subretinal fluid, hyperopia, co-existing narrow angle, and a marked decrease in electrooculogram. However, little is known about the genetic variants and specific clinical features of ARB. This is an observational case series of patients with a clinical and genetic diagnosis of ARB who underwent multimodal imaging. We describe ten patients from nine unrelated families with six known variants and three novel missense variants: c.236C\u2192T, p.(Ser79Phe); C.452C\u2192T, p.(Leu151Pro); and c.650C\u2192T, p.(Trp217Met). The most common variant was c.584C\u2192T, p.(Ala195Val), observed in six patients, without correlation to the severity of the phenotype. All patients manifested bilateral multifocal subretinal deposits and subretinal fluid throughout the follow-up period, while intraretinal fluid was found in approximately half of the eyes. The extent or chronicity of the fluid collection did not correlate with visual acuity. Angle-closure glaucoma was present in five eyes. Three patients had a genetically confirmed family history of ARB, and one patient had a clinically suspected family history. This study reveals novel mutations in the BEST1 gene and adds to the spectrum of clinical presentations of ARB.<\/jats:p>","DOI":"10.3390\/genes13071197","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T11:15:05Z","timestamp":1656933305000},"page":"1197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical Features and Genetic Findings of Autosomal Recessive Bestrophinopathy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3226-6148","authenticated-orcid":false,"given":"Hae Rang","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul 03722, Korea"},{"name":"Department of Ophthalmology, CHA Bundang Medical Center, CHA University College of Medicine, Seongnam 13496, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8607-6625","authenticated-orcid":false,"given":"Jinu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Vision Research, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8359-9618","authenticated-orcid":false,"given":"Hyun Goo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Ho","family":"Byeon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5054-9470","authenticated-orcid":false,"given":"Christopher Seungkyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"816","DOI":"10.3349\/ymj.2020.61.9.816","article-title":"Induced Pluripotent Stem Cell Modeling of Best Disease and Autosomal Recessive Bestrophinopathy","volume":"61","author":"Lee","year":"2020","journal-title":"Yonsei Med. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1399-0004.1992.tb03229.x","article-title":"The gene for Best\u2019s macular dystrophy is located at 11q13 in a Swedish family","volume":"42","author":"Forsman","year":"1992","journal-title":"Clin. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/ng0792-246","article-title":"Genetic linkage of vitelliform macular degeneration (Best\u2019s disease) to chromosome 11q13","volume":"1","author":"Stone","year":"1992","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12758","DOI":"10.1073\/pnas.220402097","article-title":"Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium","volume":"97","author":"Marmorstein","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1038\/mt.2015.177","article-title":"BEST1: The Best Target for Gene and Cell Therapies","volume":"23","author":"Yang","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00424-010-0821-5","article-title":"Bestrophins and retinopathies","volume":"460","author":"Xiao","year":"2010","journal-title":"Pflugers Arch."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.preteyeres.2009.04.002","article-title":"The spectrum of ocular phenotypes caused by mutations in the BEST1 gene","volume":"28","author":"Boon","year":"2009","journal-title":"Prog. Retin Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1159\/000290318","article-title":"\u00dcber eine heredit\u00e4re Maculaaffektion","volume":"13","author":"Best","year":"1905","journal-title":"Ophthalmologica"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Habibi, I., Falfoul, Y., Todorova, M.G., Wyrsch, S., Vaclavik, V., Helfenstein, M., Turki, A., Matri, K.E., Matri, L.E., and Schorderet, D.F. (2019). Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB). Genes, 10.","DOI":"10.3390\/genes10120953"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ajhg.2007.08.004","article-title":"Biallelic mutation of BEST1 causes a distinct retinopathy in humans","volume":"82","author":"Burgess","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8141","DOI":"10.1167\/iovs.15-18168","article-title":"A Novel BEST1 Mutation in Autosomal Recessive Bestrophinopathy","volume":"56","author":"Lee","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1016\/j.ophtha.2015.01.012","article-title":"Focal Choroidal Excavation in Multifocal Choroiditis and Punctate Inner Choroidopathy","volume":"122","author":"Kim","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1001\/jamaophthalmol.2017.4859","article-title":"Accuracy of Next-Generation Sequencing for Molecular Diagnosis in Patients With Infantile Nystagmus Syndrome","volume":"135","author":"Rim","year":"2017","journal-title":"JAMA Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.ophtha.2020.10.006","article-title":"Autosomal Recessive Bestrophinopathy: Clinical Features, Natural History, and Genetic Findings in Preparation for Clinical Trials","volume":"128","author":"Casalino","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10633-008-9154-5","article-title":"Detailed analysis of retinal function and morphology in a patient with autosomal recessive bestrophinopathy (ARB)","volume":"118","author":"Gerth","year":"2009","journal-title":"Doc. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3109\/13816810.2010.535890","article-title":"Morphological and functional changes in multifocal vitelliform retinopathy and biallelic mutations in BEST1","volume":"32","author":"Ekvall","year":"2011","journal-title":"Ophthalmol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/eye.2012.27","article-title":"A novel compound heterozygous mutation in the BEST1 gene causes autosomal recessive Best vitelliform macular dystrophy","volume":"26","author":"Zhao","year":"2012","journal-title":"Eye"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e29914","DOI":"10.7554\/eLife.29914","article-title":"Patient-specific mutations impair BESTROPHIN1\u2019s essential role in mediating Ca2+-dependent Cl- currents in human RPE","volume":"6","author":"Li","year":"2017","journal-title":"Elife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3366","DOI":"10.1167\/iovs.17-21999","article-title":"Screening of BEST1 Gene in a Chinese Cohort With Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy","volume":"58","author":"Tian","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1097\/IAE.0b013e318203ee60","article-title":"Autosomal recessive vitelliform macular dystrophy in a large cohort of vitelliform macular dystrophy patients","volume":"31","author":"Kinnick","year":"2011","journal-title":"Retina"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5332","DOI":"10.1167\/iovs.11-7174","article-title":"A homozygous frameshift mutation in BEST1 causes the classical form of Best disease in an autosomal recessive mode","volume":"52","author":"Bitner","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1001\/archophthalmol.2010.367","article-title":"Autosomal recessive best vitelliform macular dystrophy: Report of a family and management of early-onset neovascular complications","volume":"129","author":"Iannaccone","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1111\/j.1600-0420.2007.01132.x","article-title":"Intravitreal ranibizumab (Lucentis) for choroidal neovascularization associated with vitelliform macular dystrophy","volume":"86","author":"Querques","year":"2008","journal-title":"Acta Ophthalmol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/7\/1197\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:42:33Z","timestamp":1760139753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/7\/1197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,4]]},"references-count":23,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["genes13071197"],"URL":"https:\/\/doi.org\/10.3390\/genes13071197","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,4]]}}}