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TIMP3 mutation in Sorsby's fundus dystrophy: molecular insights

Published online by Cambridge University Press:  31 October 2005

Zheng Li
Affiliation:
Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle, NE4 6BH, UK.
Michael P. Clarke
Affiliation:
Department of Ophthalmology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK.
Michael D. Barker
Affiliation:
Academic Unit of Pathology, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Rd, Sheffield, S10 2RX, UK.
Norman McKie
Affiliation:
Henry Wellcome Laboratory for Biogerontology Research, Newcastle General Hospital, Newcastle, NE4 6BH, UK.

Abstract

Sorsby's fundus dystrophy (SFD) is a rare autosomal dominant disorder that results in degeneration of the macular region of the retina, with onset usually in the fourth to fifth decade of life. It leads to the rapid loss of central vision, often followed by further loss of peripheral vision. SFD shares several pathological features commonly found in the ‘wet’ or exudative form of age-related macular degeneration (AMD), the most common cause of blindness in the elderly in developed countries. These phenotypic similarities have led to SFD being proposed as an acceptable genetic model for AMD. Whereas AMD appears to have a complex aetiology, with both genetic and environmental factors playing a role, SFD has been shown to be a single-gene disorder, linked to mutations in exon 5 of the tissue inhibitor of metalloproteinases 3 (TIMP3) gene on chromosome 22q12-q13. This review confines itself to a discussion of the known biochemical properties of the wild-type and SFD TIMP3 proteins and attempts to relate these to the pathology encountered in SFD patients. We also discuss briefly how, despite the lack of inherited mutations in the structural gene, the TIMP3 protein might play a role in the onset and progression of AMD.

Type
Review Article
Copyright
© Cambridge University Press 2005

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