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. 2000 Jul;84(7):682–686. doi: 10.1136/bjo.84.7.682

Sorsby fundus dystrophy without a mutation in the TIMP-3 gene

J Assink 1, E de Backer 1, B ten 1, T Kohno 1, P T V M de Jong 1, A Bergen 1, F Meire 1
PMCID: PMC1723563  PMID: 10873973

Abstract

AIMS—To examine a large family with an autosomal dominant fundus dystrophy and to investigate whether or not mutations in TIMP-3 gene were involved.
METHODS—A large family of 58 individuals with an autosomal dominant fundus dystrophy was examined ophthalmologically. A DNA linkage analysis in the 22q12.1-q13.2 region was performed. The TIMP-3 gene was screened for mutations in all five exons.
RESULTS—In this large family 15 individuals were affected. All other individuals were found to be clinically unaffected. Pisciform flecks in the midperiphery and drusen-like deposits were the most typical ophthalmological finding in this family and were encountered from the fifth decade on. Chorioretinal atrophy and neovascularisation with disciform lesions characterised the disease from the sixth decade on. Linkage analysis using an affected only analysis, showed a maximum positive lod score of 3.94 at θ = 0.0 with marker D22S283. No mutations possibly causing Sorsby fundus dystrophy were found in either the exonic sequences, the promotor region, or the 3'UTR.
CONCLUSION—The family in this pedigree has an autosomal dominant fundus dystrophy, which is most probably Sorsby fundus dystrophy. Although, in the linkage analysis, significant positive lod scores were found with the region 22q12.1-q13.2, no causative mutations could be identified in the TIMP-3 gene.



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Figure 1  .

Figure 1  

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Pedigree of the family with Sorsby fundus dystrophy. Males are represented by squares and females are represented by circles; solid symbols represent individuals with Sorsby fundus dystrophy, open symbols represent normal individuals. A cross represents the individuals who were clinically examined and used for linkage analysis.

Figure 2  .

Figure 2  

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(A) Pisciform flecks at the posterior pole (patient III,29). (B) Flecks nasally to the pupil (patient III,29). (C) Drusen-like deposits (patient III,31). (D) Extensive chorioretinal atrophy (patient III,9). (E) Choroidal neovascularisation with haemorrhages and exudation (patient III,7). (F) Disciform lesion with fibrotic reaction extending far outside the macula (patient II,8 right eye). (G) Pisciform flecks at the arcades, atrophic patches surrounding the macula (patient II,8 left eye).

Figure 3  .

Figure 3  

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(A) Patient III,9 at the age of 60 years; left eye visual acuity 0.2, notice atrophy of the capillary. (B) Same patient (III,9) at the age of 63; left eye visual acuity decreased to light perception due to involvement of the macula by the choriocapillary atrophy.

Figure 4  .

Figure 4  

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(A) Sequence of exon 5 in an affected individual with Sorsby fundus dystrophy. (B) Nucleotide sequence and sequence of the conceptual translation product of exon 5. For previously described mutations, the replacing amino acid is shown underneath the consensus amino acid.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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