Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy

Samuel G Jacobson; Artur V Cideciyan; Jean Bennett; Ronald M Kingsley; Val C Sheffield; Edwin M Stone

doi:10.1001/archopht.120.3.376

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Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy

Journal article

Peer reviewed

Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy

Samuel G Jacobson, Artur V Cideciyan, Jean Bennett, Ronald M Kingsley, Val C Sheffield and Edwin M Stone

Archives of ophthalmology (1960), Vol.120(3), pp.376-379

03/2002

DOI: 10.1001/archopht.120.3.376

PMID: 11879143

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Abstract

To determine the molecular basis of a retinopathy previously described as dominant macular subretinal neovascularization with peripheral retinal degeneration. The TIMP3 gene was analyzed in family members, and 4 mutation-positive patients were studied using psychophysics and electroretinography. Cosegregating with disease in the family was a single base pair change in the TIMP3 gene, altering a conserved tyrosine to cysteine at amino acid position 172 (Y172C). There was psychophysical and electroretinographic evidence of rod dysfunction greater than cone dysfunction. Dark adaptometry showed abnormalities with regional retinal variation in degree. The Y172C mutation in the TIMP3 gene is another cause of Sorsby fundus dystrophy. The expression of this form of the disease, as in other C-terminal TIMP3 mutations, is speculated to be secondary to mutant TIMP-3, causing a decreased turnover of the extracellular matrix. The molecular clarification of inherited retinal degeneration involving abnormal extracellular matrix turnover in and around Bruch's membrane should provide clues to the pathogenesis of not only these particular diseases but also forms of age-related macular degeneration.

Polymerase Chain Reaction

Mutation

Electroretinography

Retinal Degeneration - genetics

Humans

Middle Aged

Male

Dark Adaptation

Polymorphism, Single-Stranded Conformational

Pedigree

Adolescent

Adult

Female

Visual Field Tests

Eye Proteins - genetics

Retinal Degeneration - pathology

Child

Fundus Oculi

Tissue Inhibitor of Metalloproteinase-3 - genetics

Details

Title: Subtitle: Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy
Creators: Samuel G Jacobson - Scheie Eye Institute, 51 N 39th St, Philadelphia, PA 19104, USA. jacobsos@mail.med.upenn.edu
Artur V Cideciyan
Jean Bennett
Ronald M Kingsley
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Archives of ophthalmology (1960), Vol.120(3), pp.376-379
DOI: 10.1001/archopht.120.3.376
PMID: 11879143
NLM abbreviation: Arch Ophthalmol
ISSN: 0003-9950
eISSN: 1538-3601
Publisher: American Medical Association; United States
Grant note: EY13203 / NEI NIH HHS EY12156 / NEI NIH HHS EY-05627 / NEI NIH HHS
Language: English
Date published: 03/2002
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983980041802771

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