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

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.

Publication metadata

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

Year: 2001

Volume: 85

Issue: 12

Pages: 1429-1431

ISSN (print): 0007-1161

ISSN (electronic):

Publisher: BMJ Group


DOI: 10.1136/bjo.85.12.1429


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