A novel splice site mutation in the tissue inhibitor of the metalloproteinases-3 gene in Sorsby’s fundus dystrophy with unusual clinical features |
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Authors: | Yoshiaki Tabata Yasushi Isashiki Kousaku Kamimura Kumiko Nakao N Ohba |
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Institution: | (1) Department of Ophthalmology, Kagoshima University Faculty of Medicine, Kagoshima-shi 890, Japan e-mail: ohba@med5.kufm.kagoshima-u.ac.jp, Tel.: +81 099 2755402, Fax: +81 099 2641387, JP;(2) Center for Chronic Viral Diseases, Kagoshima University Faculty of Medicine, Kagoshima-shi 890-8520, Japan, JP |
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Abstract: | Sorsby’s fundus dystrophy (SFD) is an autosomal dominant macular dystrophy which is developed usually in the third or fourth
decade of life, and is characterized by central visual loss and nyctalopia due to fundus changes of exudative or atrophic
macular lesions. Its functional prognosis is usually poor because of disciform macular scars and peripheral chorioretinal
atrophies. To date, five different mutations in the tissue inhibitor of the metallo-proteinases-3 (TIMP3) gene have been identified
in families of a wide geographic origin, all of which are missense mutations that cause replacement by cysteine of conserved
amino acids in the C-terminus of exon 5 of TIMP3. We have studied two Japanese families with SFD, the first report from the
Eastern world, and identified a novel 3’ splice site mutation in the TIMP3 gene, namely a single base insertion at the intron
4/exon 5 junction which converts the consensus sequence CAG to CAAG in the splice acceptor site. In addition, our patients
displayed a distinctive clinical expression in that they developed macular dystrophies at an approximately 30-year later age
of onset and preserved functional vision until later life with essentially uninvolved peripheral retina. The present findings
may provide some insight into the genotype–phenotype relationship in SFD.
Received: 27 March 1998 / Accepted: 2 May 1998 |
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