Assessment of mutations in the best macular dystrophy (VMD2) gene in patients with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and bull’s-eye maculopathy1☆,
Section snippets
Materials and methods
The Family Macular Degeneration Study is a National Institutes of Health-supported, Massachusetts Eye and Ear Infirmary Human Subject Committee-approved study being performed to determine the genetic basis of macular degeneration. As part of this study, patients are asked questions about their family members, and a complete pedigree is constructed. All participants consent to a thorough ocular evaluation with fundus photography, which may also include diagnostic testing when appropriate
Patient 1
A 72-year-old male noted mild gradual visual deterioration over a 13-year period. The patient reported no family history of eye problems or visual loss. In February 1995, his visual acuity was recorded as 20/25 in each eye. His anterior segment examination results were within normal limits. Funduscopic examination revealed large confluent drusen and hypopigmentation and clumping of RPE in both eyes. There was no evidence of basal laminar drusen in either eye. Fluorescein angiography
Discussion
Four unique variants were detected in the VMD2 (Best) gene in 5 patients with maculopathies: 3 of 259 subjects (approximately 1%) with age-related maculopathy, and 2 of 28 other subjects (approximately 7%) with maculopathies not diagnosed as classic Best disease. These two latter cases with genetic variants in VMD2 included one of three subjects with adult-onset foveomacular vitelliform maculopathy and one of five subjects with bull’s-eye maculopathy. It is interesting to note that three of
Acknowledgements
The authors thank the patients and the referring physicians, without whose cooperation this work would not have been possible.
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2021, Journal of Lipid ResearchCitation Excerpt :The protein, human Best1 (hBest1), encoded by this gene, is an integral membrane protein found primarily in the RPE, which functions as an anion channel (332–334). Mutations in the BEST1 gene have been uncovered as the cause of several other ocular diseases, including adult-onset macular dystrophy and bull’s eye maculopathy (335). In addition to a nonfunctional hBest1 protein, disruption of processes that regulate hBest1 function can also lead to retinopathies.
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2020, American Journal of OphthalmologyCitation Excerpt :Thirty-seven BEST1 mutations were detected in 53 vitelliform macular dystrophy patients in our study. The mutation detection rate was 40% (53/134) in total, 45% in BVMD patients, 82% in ARB or ARB-like patients, and 0% in AVMD patients, which is in accordance with previous reports showing that the mutation rate was around 50%-86% in BVMD patients,13,29,31,39,42 100% in ARB patients,2,36 and 0%-33% in AVMD patients.29,43 The majority of BEST1 mutations (32/37) in our patients were missense mutations, which was also consistent with previous studies.1,12
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- ☆
Supported in part by the National Eye Institute, Bethesda, Maryland (grant nos.: EY11309 [JMS] and EY11600 [PSB]; Research to Prevent Blindness, Inc., New York, New York; an RPB Lew R. Wasserman Merit Award (JMS); an RPB career development award (PSB and RA); the Lions Eye Research Fund, Inc., Northboro, Mass., an unrestricted grant to Moran Eye Center; and The Ruth and Milton Steinbach Fund, New York, NY.
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The authors have no proprietary interest in the products or devices mentioned herein.