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Z. Saihan, Z. Li, J. Rice, C.P. J. Blyth, S. Ramsden, G.C. Black, N. McKie, A.R. Webster; A Novel TIMP3 Mutation and in vivo Imaging of a Family With Sorsby Fundus Dystrophy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4610.
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© ARVO (1962-2015); The Authors (2016-present)
To characterise and report a family with Sorsby’s fundus dystrophy (SFD) with a novel mutation in the TIMP3 gene
The TIMP3 gene was analysed in a family and 3 mutation positive patients were studied with regard to their visual function and retinal imaging using colour fundus photography, scanning laser ophthalmoscope and optical coherence tomography. The mutant variant was expressed in ARPE19 and COS7 cells and assayed for inhibitory activity and oligomerisation.
A single base pair change (G>A 484) resulting in a glycine to a leucine at amino acid position 162 (E162K) was found to co segregate with the disease. This change was not found in a panel of 534 control chromosomes. The E162K change was affected by standard site–directed mutagenesis techniques in the wild–type protein sequence. Fundal retinal images show intrafamilial variability with regard to amount of drusenlike deposits throughout the retina as well as the amount of visible sub–retinal deposit. In all cases OCT–3 images demonstrate a hyper–reflective RPE–photoreceptor / choroid complex which may be due to the deposition of abnormal protein related to expression of the mutant TIMP–3 protein within Bruch’s membrane as previously reported in this condition.
The E162K mutation is another cause of Sorsby fundus dystrophy. In vivo imaging techniques such as optical coherence tomography provide important information regarding the pathophysiology of SFD and could potentially be used as a diagnostic aid.
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