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Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism

Clarke, M., Mitchell, K.W., Goodship, J., McDonnell, S., Barker, M.D., Griffiths, I.D. and McKie, N. (2001) Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism. British Journal of Ophthalmology, 85 (12). pp. 1429-1431. ISSN 1468-2079


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AIMS: To describe the phenotype in three family members affected by a novel mutation in the gene coding for the enzyme tissue inhibitor of metalloproteinase-3 (TIMP-3). METHODS: Three members of the same family were seen with a history of nyctalopia and visual loss due to maculopathy. Clinical features were consistent with Sorsby's fundus dystrophy. Exon 5 of the gene coding for TIMP-3 was amplified by the polymerase chain reaction, single strand conformation polymorphism analysis undertaken and exon 5 amplicons were directly sequenced. RESULTS: Onset of symptoms was in the third to fourth decade. Five of six eyes had geographic macular atrophy rather than neovascularisation as a cause for central visual loss. Peripheral retinal pigmentary disturbances were present. Scotopic ERGs were abnormal in all three. Mutation analysis showed a GT transversion in all three resulting in a premature termination codon, E139X, deleting most of the carboxy terminal domain of TIMP-3. CONCLUSIONS: The patients described had a form of Sorsby's fundus dystrophy which fell at the severe end of the spectrum of this disease. Postulated disease mechanisms include deposition of dimerised TIMP-3 protein.

Item Type: Article
Copyright, Publisher and Additional Information: © 2001 by British Journal of Ophthalmology
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology (Sheffield)
Depositing User: Repository Officer
Date Deposited: 24 Feb 2005
Last Modified: 04 Jun 2014 20:21
Published Version: http://bjo.bmjjournals.com/cgi/content/full/85/12/...
Status: Published
Refereed: Yes
Identification Number: 10.1136/bjo.85.12.1429
URI: http://eprints.whiterose.ac.uk/id/eprint/300

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