Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular Dystrophy
Abstract Adult-onset vitelliform macular dystrophy (AVMD) is a common and benign macular degeneration which can be caused by BEST1 mutation. Here, we investigated the clinical characteristics associated with a newly identified BEST1 mutation, p.Ile38Ser and confirmed the associated physiological fun...
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-09629-9 |
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| author | Ikhyun Jun Joon Suk Lee Ji Hwan Lee Christopher Seungkyu Lee Seung-il Choi Heon Yung Gee Min Goo Lee Eung Kweon Kim |
| author_facet | Ikhyun Jun Joon Suk Lee Ji Hwan Lee Christopher Seungkyu Lee Seung-il Choi Heon Yung Gee Min Goo Lee Eung Kweon Kim |
| author_sort | Ikhyun Jun |
| collection | DOAJ |
| description | Abstract Adult-onset vitelliform macular dystrophy (AVMD) is a common and benign macular degeneration which can be caused by BEST1 mutation. Here, we investigated the clinical characteristics associated with a newly identified BEST1 mutation, p.Ile38Ser and confirmed the associated physiological functional defects. The 51-year-old patient presented bilateral small subretinal yellow deposits. Consistent with AVMD, the corresponding lesions showed hyperautofluorescence, late staining in fluorescein angiography, and subretinal hyper-reflective materials in spectral-domain optical coherence tomography. Genetic analysis demonstrated that the patient presented with a heterozygous p.Ile38Ser BEST1 mutation. Surface biotinylation and patch clamp experiments were performed in transfected HEK293T cells. Although, the identified BEST1 mutant maintains normal membrane expression, p.Ile38Ser mutant showed significantly smaller currents than wild type (WT). However, it showed larger currents than other BEST1 mutants, p.Trp93Cys, causing autosomal dominant best vitelliform macular dystrophy (BVMD), and p.Ala195Val, causing autosomal recessive bestrophinopathy (ARB). The cells expressing both WT and each BEST1 mutant showed that the functional defect of p.Ile38ser was milder than that of p.Trp93Cys, whereas combination of p.Ala195Val with WT showed good current. We identified and described the phenotype and in vitro functions of a novel BEST1 mutation causing AVMD. AVMD induced by p.Ile38Ser BEST1 mutation is a mild form of BVMD. |
| first_indexed | 2024-12-20T20:44:15Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-20T20:44:15Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-c613dde51467479aa4529965d8eacc792022-12-21T19:27:05ZengNature PortfolioScientific Reports2045-23222017-08-017111110.1038/s41598-017-09629-9Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular DystrophyIkhyun Jun0Joon Suk Lee1Ji Hwan Lee2Christopher Seungkyu Lee3Seung-il Choi4Heon Yung Gee5Min Goo Lee6Eung Kweon Kim7The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of MedicineDepartment of Pharmacology and Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineThe Institute of Vision Research, Department of Ophthalmology, Yonsei University College of MedicineThe Institute of Vision Research, Department of Ophthalmology, Yonsei University College of MedicineCorneal Dystrophy Research Institute, Yonsei University College of MedicineDepartment of Pharmacology and Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineDepartment of Pharmacology and Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of MedicineThe Institute of Vision Research, Department of Ophthalmology, Yonsei University College of MedicineAbstract Adult-onset vitelliform macular dystrophy (AVMD) is a common and benign macular degeneration which can be caused by BEST1 mutation. Here, we investigated the clinical characteristics associated with a newly identified BEST1 mutation, p.Ile38Ser and confirmed the associated physiological functional defects. The 51-year-old patient presented bilateral small subretinal yellow deposits. Consistent with AVMD, the corresponding lesions showed hyperautofluorescence, late staining in fluorescein angiography, and subretinal hyper-reflective materials in spectral-domain optical coherence tomography. Genetic analysis demonstrated that the patient presented with a heterozygous p.Ile38Ser BEST1 mutation. Surface biotinylation and patch clamp experiments were performed in transfected HEK293T cells. Although, the identified BEST1 mutant maintains normal membrane expression, p.Ile38Ser mutant showed significantly smaller currents than wild type (WT). However, it showed larger currents than other BEST1 mutants, p.Trp93Cys, causing autosomal dominant best vitelliform macular dystrophy (BVMD), and p.Ala195Val, causing autosomal recessive bestrophinopathy (ARB). The cells expressing both WT and each BEST1 mutant showed that the functional defect of p.Ile38ser was milder than that of p.Trp93Cys, whereas combination of p.Ala195Val with WT showed good current. We identified and described the phenotype and in vitro functions of a novel BEST1 mutation causing AVMD. AVMD induced by p.Ile38Ser BEST1 mutation is a mild form of BVMD.https://doi.org/10.1038/s41598-017-09629-9 |
| spellingShingle | Ikhyun Jun Joon Suk Lee Ji Hwan Lee Christopher Seungkyu Lee Seung-il Choi Heon Yung Gee Min Goo Lee Eung Kweon Kim Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular Dystrophy Scientific Reports |
| title | Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular Dystrophy |
| title_full | Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular Dystrophy |
| title_fullStr | Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular Dystrophy |
| title_full_unstemmed | Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular Dystrophy |
| title_short | Adult-Onset Vitelliform Macular Dystrophy caused by BEST1 p.Ile38Ser Mutation is a Mild Form of Best Vitelliform Macular Dystrophy |
| title_sort | adult onset vitelliform macular dystrophy caused by best1 p ile38ser mutation is a mild form of best vitelliform macular dystrophy |
| url | https://doi.org/10.1038/s41598-017-09629-9 |
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