Purpose: To perform a genotype-phenotype correlation for three patients heterozygous for a missense mutation in the tissue inhibitor of metalloproteinase 3 (TIMP3) gene.
Methods: Retrospective, observational case series. The medical records and photographs were reviewed for three patients diagnosed at the time with neovascular age-related macular degeneration (AMD). All were later found to carry a predicted C113G mutation in the TIMP3 gene, other known mutations in which are associated with Sorsby's fundus dystrophy.
Results: All three patients developed drusen and bilateral choroidal neovascularisation with subsequent disciform scarring and atrophy. Visual acuity rapidly deteriorated to <6/60 in both eyes. The age of onset varied from 56 to 64 years and the interval to contralateral eye involvement varied from 4 to 6 years. Two of the three patients had a family history of AMD. All three patients were heterozygous for the C113G nucleotide change, resulting in a Ser38Cys change at the N terminus of the TIMP3 protein.
Conclusion: This case series suggests the C113G TIMP3 variant may represent a novel highly penetrant mutation causing choroidal neovascularisation of relatively late onset for Sorsby's fundus dystrophy, mimicking early onset AMD.