Autosomal dominant hemorrhagic macular dystrophy not associated with the TIMP3 gene.
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 haplo-type 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.


CONCLUSIONS
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.
Ayyagari
R
R
W.K. Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA. ayyagari@umich.edu
Griesinger
I B
IB
Bingham
E
E
Lark
K K
KK
Moroi
S E
SE
Sieving
P A
PA
D000328:Adult; D000368:Aged; D003119:Color Perception Tests; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005091:Exons; D005260:Female; D005451:Fluorescein Angiography; D008040:Genetic Linkage; D006068:Gonioscopy; D006239:Haplotypes; D006801:Humans; D008268:Macular Degeneration / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012166:Retinal Hemorrhage / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*; D014794:Visual Fields
D019717:Tissue Inhibitor of Metalloproteinase-3