A rare penetrant TIMP3 mutation confers relatively late onset choroidal neovascularisation which can mimic age-related macular degeneration.
OBJECTIVE
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.


CONCLUSIONS
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.
Clinical Neurosciences Research Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|Eye Unit, University Southampton NHS Trust, Southampton, UK.
A
A
Warwick
Centre for Biological Science, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK.
J
http://orcid.org/0000-0002-0973-8285
J
Gibson
Centre for Biological Science, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK.
R
R
Sood
Clinical Neurosciences Research Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|Eye Unit, University Southampton NHS Trust, Southampton, UK.
A
http://orcid.org/0000-0001-5541-4305
A
Lotery
D020256:Choroidal Neovascularization / Q000175:diagnosis* / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D005451:Fluorescein Angiography; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D015593:Retinal Drusen / Q000175:diagnosis / Q000235:genetics; D012189:Retrospective Studies; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000175:diagnosis*
C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3