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

A rare penetrant TIMP3 mutation confers relatively late onset choroidal neovascularisation which can mimic age-related macular degeneration
A rare penetrant TIMP3 mutation confers relatively late onset choroidal neovascularisation which can mimic age-related macular degeneration
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.
0950-222X
2-4
Warwick, A.
eab9cc60-6a67-48a7-9210-580756aa17a7
Gibson, J.
855033a6-38f3-4853-8f60-d7d4561226ae
Sood, R.
5ca793d0-ce4a-48e6-a646-b1348ac4219f
Lotery, A.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Warwick, A.
eab9cc60-6a67-48a7-9210-580756aa17a7
Gibson, J.
855033a6-38f3-4853-8f60-d7d4561226ae
Sood, R.
5ca793d0-ce4a-48e6-a646-b1348ac4219f
Lotery, A.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514

Warwick, A., Gibson, J., Sood, R. and Lotery, A. (2015) A rare penetrant TIMP3 mutation confers relatively late onset choroidal neovascularisation which can mimic age-related macular degeneration. Eye, 2-4. (doi:10.1038/eye.2015.204). (PMID:26493035)

Record type: Article

Abstract

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.

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Warwick et al_Eye_2015_TIMP3.pdf - Accepted Manuscript
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More information

Accepted/In Press date: 3 September 2015
e-pub ahead of print date: 23 October 2015
Organisations: Centre for Biological Sciences, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 384127
URI: https://eprints.soton.ac.uk/id/eprint/384127
ISSN: 0950-222X
PURE UUID: fad33356-079c-4caf-95cb-5e1f056e4b04
ORCID for J. Gibson: ORCID iD orcid.org/0000-0002-0973-8285
ORCID for A. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

Catalogue record

Date deposited: 17 Nov 2015 15:31
Last modified: 31 Jan 2019 01:36

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Contributors

Author: A. Warwick
Author: J. Gibson ORCID iD
Author: R. Sood
Author: A. Lotery ORCID iD

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