Cited by 656Retinal Development and DisordersRetinal Diseases and TreatmentsProtease and Inhibitor Mechanisms

Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy

Weber, Bernhard H. F., Vogt, Gudrun, Pruett, Ronald C., Stöhr, Heidi, Felbor, Ute·1994·Nature Genetics

Abstract

The hereditary macular dystrophies are progressive degenerations of the central retina and contribute significantly to irreversible visual loss in developed countries. Among these disorders, Sorsby's fundus dystrophy (SFD), an autosomal dominant condition, provides an excellent mendelian model for the study of the genetically complex age-related macular degeneration (AMD), the most common maculopathy in the elderly. Recently, we mapped the SFD locus to 22q13-qter. This same region contains the gene for tissue inhibitor of metalloproteinases-3 (TIMP3), which is known to play a pivotal role in extracellular matrix remodeling. We have now identified point mutations in the TIMP3 gene in affected members of two SFD pedigrees. These mutations are predicted to disrupt the tertiary structure and thus the functional properties of the mature protein.

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Crossref · 10.1038/ng1294-352

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Authors
Weber, B. H. F., Vogt, G., Pruett, R. C., Stöhr, H., & Felbor, U.
Affiliations
University of Würzburg (DE)
Venue
Nature Genetics
Published
1994-12
Volume
8
Issue
4
Pages
352-356
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W1990509128
Cited by
656
References
33
Citations by year
2026: 3 · 2025: 9 · 2024: 10 · 2023: 11 · 2022: 11 · 2021: 12 · 2020: 11 · 2019: 13 · 2018: 12 · 2017: 20 · 2016: 11 · 2015: 13 · 2014: 14 · 2013: 17 · 2012: 16
FWCI
15.19
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
Sorsby's fundus dystrophy, TIMP-3, point mutations, hereditary macular dystrophy, autosomal dominant inheritance, extracellular matrix remodeling, protein tertiary structure, age-related macular degeneration, gene mapping
MeSH terms
Amino Acid Sequence, Base Sequence, Chromosome Mapping, Chromosomes, Human, Pair 22, Exons, Female, Humans, Macular Degeneration, Male, Metalloendopeptidases, Molecular Sequence Data, Neoplasm Proteins, Pedigree, Polymorphism, Genetic, Point Mutation, Tissue Inhibitor of Metalloproteinase-3

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