Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism. Issue 12 (1st December 2001)

• Record Type: Journal Article
• Authors: Clarke, Michael; Mitchell, Keith W; Goodship, Judith; McDonnell, Sharon; Barker, Michael D; Griffiths, Ian D; McKie, Norman
• Is Part Of: British journal of ophthalmology. Volume 85:Issue 12(2001)
• Page Start: 1429
• Page End: 1431
• Publication Date: 2001-12-01
• Subjects: macula -- TIMP-3 -- Sorsby's fundus dystrophy; Ophthalmology -- Periodicals; 617.7
• DOI: 10.1136/bjo.85.12.1429
• Languages: English
• ISSNs: 0007-1161

Abstract

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.