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Lookup NU author(s): Michael Clarke,
Dr Keith Mitchell,
Professor Judith Goodship
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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 G -->T 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.
Author(s): Goodship J; Clarke M; Mitchell KW; McDonnell S; Barker MD; Griffiths ID; McKie N
Publication type: Article
Publication status: Published
Journal: British Journal of Ophthalmology
ISSN (print): 0007-1161
Publisher: BMJ Group
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