Autosomal Dominant Hemorrhagic Macular Dystrophy Not Associated With the TIMP3 Gene

Abstract

To describe the ophthalmic and genetic findings of a large kindred (UM:H389) with autosomal dominant hemorrhagic macular dystrophy. Methods: The disease state of family members was documented by dilated fundus examination, electroretinography, color vision tests, fluorescein angiography, measurement of visual fields, biomicroscopy, gonioscopy, and intraocular pressure measurement. Linkage and haplotype analyses were carried out with markers flanking the Sorsby fundus dystrophy TIMP3 (tissue inhibitor of metalloproteinase 3) gene locus, and mutation analysis was carried out by screening exon 5 of the TIMP3 gene. Results: This 4-generation pedigree with autosomal dominant hemorrhagic macular degeneration has visual symptoms beginning in the sixth decade of life. Several family members developed choroidal neovascular membrane formation in the macula of both eyes. The phenotype overlaps that of Sorsby fundus dystrophy. Some of the affected members have unusual zonularlike radial striations on the anterior lens capsule surface, and glaucoma or ocular hypertension has developed in 2 of them. Involvement of the TIMP3 gene was excluded by linkage, haplotype, and mutation analyses. Conclusions: The phenotype of this family with autoso-maldominantmaculardystrophyoverlapsthatofSorsbyfundus dystrophy. Exclusion of the TIMP3 gene in this family indicatesgeneticheterogeneityforhemorrhagicmaculardystrophy.Anteriorsegmentanomaliesmayoccurwiththiscondition, but cosegregation has not yet been established. Clinical Relevance: This study broadens the spectrum of hemorrhagic macular dystrophy by identifying a family in which the TIMP3 gene is not involved. Once the gene is cloned, we are eager to learn whether this gene may be involved in age-related macular degeneration.

Late-Onset Autosomal Dominant Macular Dystrophy with Choroidal Neovascularization and Nonexudative Maculopathy Associated with Mutation in theRDSGene

“…6 Most families and patients described with late-onset exudative phenotype either have been linked to a TIMP3 locus or carry a mutation in the TIMP3 gene, except for a family that we described earlier. [12][13][14] We recently identified another large family (SUNY901) whose members have an unusual late-onset maculopathy with exudative and atrophic features. After excluding most of the previously described macular disease loci including the loci for exudative fundus dystrophies and AMD, 5,7,[15][16][17] we mapped the disease locus to a 9-centimorgan (cM) interval on chromosome 6.…”

Alterations of the Tissue Inhibitor of Metalloproteinase-3 (TIMP3) Gene in Pancreatic Adenocarcinomas

“…24,25 Because we 13 and others 12,26 did not detect any TIMP3 mutations in other solid tumors such as endocrine pancreatic tumors and kidney cancers, one would not expect these mechanisms to play a major role in pancreatic carcinoma. PCR-based detection of homozygous deletion is complicated in primary tumor specimens due to the presence of admixed nonneoplastic tissue.…”

Treatment of a choroidal neovascular membrane in a patient with late-onset retinal degeneration (L-ORD) with intravitreal Ranibizumab

“…Fundus fluorescein angiography (FFA) showed a juxtafoveal classic CNV ( Figure 1) and optical coherence tomography (OCT) confirmed intra-retinal oedema over the area of the CNV (Figure 1). Owing to the reported poor outcome from the use of focal argon laser photocoagulation in such cases, 1 the patient received an intravitreal injection of Ranibizumab (0.5 mg). This was followed by two further injections at 4-weekly intervals.…”

“…4 If untreated, the natural history of the lesions is poor. 1 To date, only laser photocoagulation of lesions in three eyes has been reported, with poor results. 1 We report the successful 12-month outcome of a juxtafoveal CNV treated with intravitreal Ranibizumab.…”

“…1 To date, only laser photocoagulation of lesions in three eyes has been reported, with poor results. 1 We report the successful 12-month outcome of a juxtafoveal CNV treated with intravitreal Ranibizumab. Closure of the lesion was achieved after three treatments, with stabilisation of vision and no evidence of recurrence at month 12.…”