This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (4)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Ophthalmology, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

Radha Ayyagari, PhD; Irina B. Griesinger, PhD; Eve Bingham; Kurt K. Lark, MD; Sayoko E. Moroi, MD, PhD; Paul A. Sieving, MD, PhD

Arch Ophthalmol. 2000;118:85-92.

Objective  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 autosomal dominant macular dystrophy overlaps that of Sorsby fundus dystrophy. Exclusion of the TIMP3 gene in this family indicates genetic heterogeneity for hemorrhagic macular dystrophy. Anterior segment anomalies may occur with this condition, 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.

From the W. K. Kellogg Eye Center, University of Michigan, Ann Arbor.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Late-onset retinal macular degeneration: clinical insights into an inherited retinal degeneration
Borooah et al.
Postgrad. Med. J. 2009;85:495-500.
ABSTRACT | FULL TEXT  

Late-onset retinal macular degeneration: clinical insights into an inherited retinal degeneration
Borooah et al.
Br J Ophthalmol 2009;93:284-289.
ABSTRACT | FULL TEXT  

CTRP5 Is a Membrane-Associated and Secretory Protein in the RPE and Ciliary Body and the S163R Mutation of CTRP5 Impairs Its Secretion
Mandal et al.
IOVS 2006;47:5505-5513.
ABSTRACT | FULL TEXT  

Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5
Shu et al.
Hum Mol Genet 2006;15:1680-1689.
ABSTRACT | FULL TEXT  

Late-Onset Macular Degeneration and Long Anterior Lens Zonules Result from a CTRP5 Gene Mutation
Ayyagari et al.
IOVS 2005;46:3363-3371.
ABSTRACT | FULL TEXT  

Late-Onset Autosomal Dominant Macular Dystrophy with Choroidal Neovascularization and Nonexudative Maculopathy Associated with Mutation in the RDS Gene
Khani et al.
IOVS 2003;44:3570-3577.
ABSTRACT | FULL TEXT  

Frequent Methylation-Associated Silencing of the Tissue Inhibitor of Metalloproteinase-3 Gene in Pancreatic Endocrine Tumors
Wild et al.
J. Clin. Endocrinol. Metab. 2003;88:1367-1373.
ABSTRACT | FULL TEXT