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A de novo MYOC mutation detected in juvenile open angle glaucoma associated with reduced myocilin protein in aqueous humor |
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| Authors: | John Kuchtey Uttio Roy Chowdhury Colby C Uptegraft Michael P Fautsch Rachel W Kuchtey |
| Institution: | 1. Vanderbilt Eye Institute, Vanderbilt University, 2311 Pierce Avenue, Nashville, TN 37232, USA;2. Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA;1. Department of Psychological and Brain Sciences, Indiana University Bloomington, 1101 East 10th Street, Bloomington, IN 47405, USA;2. Department of Psychiatry, Indiana University School of Medicine, 1111 West 10th Street, Indianapolis, IN 46202, USA;3. Larue D. Carter Memorial Hospital, 2601 Cold Springs Road, Indianapolis, IN 46222, USA;1. Department of Internal Medicine and Endocrinology, Aarhus University Hospital, Aarhus, Denmark;2. Section of Epidemiology, Department of Public Health, Aarhus University Hospital, Aarhus, Denmark;3. Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark;1. Kittner Eye Center, University of North Carolina Hospitals, 5151 Bioinformatics Bldg, CB #7040, Chapel Hill, NC 27599-7040, USA;2. Vance Thompson Vision, University of South Dakota Medical Center, USA;3. Department of Ophthalmology, Mayo Clinic, USA;4. Duke University Eye Center, USA |
| Abstract: | MYOC mutations were originally identified in patients with juvenile open angle glaucoma (JOAG). Cell culture and mouse studies suggest that MYOC mutations cause glaucoma through a dominant-negative effect on myocilin protein secretion. We tested this hypothesis with patient samples in this study. Glaucoma and control patients underwent complete ocular examination. DNA samples from glaucoma patients, unaffected relatives and controls were used for DNA sequencing of MYOC. Aqueous humor (AH) samples from glaucoma and control patients were obtained at the time of surgery. Myocilin protein in AH was detected by quantitative Western blot analysis. A de novo Val251Ala mutation of MYOC was found to segregate with disease in a family with autosomal dominant JOAG. Myocilin protein was detected in all control AH samples but was nearly undetectable in AH samples from a patient heterozygous for the Val251Ala mutation. Our results using human patient samples are consistent with a dominant-negative effect of pathogenic MYOC mutations on myocilin secretion. |
| Keywords: | Aqueous humor Glaucoma Myocilin |
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