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.
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.
Authors: T Takahashi; T Nakamura; A Hayashi; M Kamei; M Nakabayashi; A A Okada; N Tomita; Y Kaneda; Y Tano Journal: Am J Ophthalmol Date: 2000-12 Impact factor: 5.258
Authors: J A Vranka; E Johnson; X Zhu; A Shepardson; J P Alexander; J M Bradley; M K Wirtz; R G Weleber; M L Klein; T S Acott Journal: Curr Eye Res Date: 1997-02 Impact factor: 2.424
Authors: R A Williamson; F A Marston; S Angal; P Koklitis; M Panico; H R Morris; A F Carne; B J Smith; T J Harris; R B Freedman Journal: Biochem J Date: 1990-06-01 Impact factor: 3.857
Authors: S G Jacobson; A V Cideciyan; G Regunath; F J Rodriguez; K Vandenburgh; V C Sheffield; E M Stone Journal: Nat Genet Date: 1995-09 Impact factor: 38.330
Authors: Kumar S D Kothapalli; Joshua C Anthony; Bruce S Pan; Andrea T Hsieh; Peter W Nathanielsz; J Thomas Brenna Journal: PLoS One Date: 2007-04-11 Impact factor: 3.240