A novel mutation at the N-terminal domain of the TIMP3 gene in Sorsby fundus dystrophy.

PURPOSE: To report a novel mutation occurring in the N-terminal domain of the tissue inhibitor of metalloproteinase 3 (TIMP3) gene in Sorsby fundus dystrophy.

METHODS

Retrospective review of medical records of two patients who had clinical features consistent with Sorsby fundus dystrophy. Genetic testing confirmed a mutation in the TIMP3 gene in both patients.

RESULTS

Both patients had findings of drusenlike deposits, retinal pigment epithelial and photoreceptor atrophy, and bilateral, recurrent choroidal neovascularization. A strong family history of early onset macular degeneration was present in both. The patients developed choroidal neovascularization at the age of 45 and 48 years, and both had multiple recurrences in both eyes. Genetic testing in both patients confirmed a heterozygous nucleotide change of C113G, causing a Ser38Cys change in Exon 1 of the N-terminal domain of the TIMP3 gene.

CONCLUSION

All previously reported mutations in Sorsby fundus dystrophy occur at Exon 5 in the C-terminal domain. We report 2 patients with novel mutations in Exon 1 of the N-terminal domain. Although the mutation occurs at a different location on the TIMP3 gene, the clinical features are similar to other reported patients with Sorsby fundus dystrophy. This finding assists in understanding the pathogenesis of this disorder.