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. 2001 Dec;85(12):1429–1431. doi: 10.1136/bjo.85.12.1429

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

M Clarke 1, K Mitchell 1, J Goodship 1, S McDonnell 1, M Barker 1, I Griffiths 1, N McKie 1
PMCID: PMC1723822  PMID: 11734514

Abstract

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.



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Figure 1  .

Figure 1  

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Patient IV:4. (A) Right fundus. (B) Right fundus fluorescein angiogram, transit phase.

Figure 2  .

Figure 2  

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Photopic flash and flicker; and scotopic flash full field ERGs of patient IV:10 and age matched control.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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