Sorsby's fundus dystrophy - A South African family with a point mutation on the tissue inhibitor of metalloproteinases-3 gene on chromosome

Purpose: The authors studied the variable expressivity of the phenotype and molecular genetics of a South African family with the fundus appearance of Sorsby's fundus dystrophy. Methods: Seventeen members of a single family underwent examination. Five of these were affected. Clinical details of five other affected family members were obtained from their ophthalmologists. Patients were questioned about age of onset, history of night blindness, and color defects. Examination included fundoscopy, color testing, color photographs, and fluorescein angiography. Blood for molecular genetic analysis was taken from 23 family members. Results: The age of onset of symptoms was 29 to 56 years, and the rate of progression was variable. Sudden decreased vision was associated with subretinal choroidal neovascularization. Slower visual decline was associated with central chorioretinal atrophy. Progressive retinal pigment epithelial atrophy and peripheral pigment clumping occurred in elderly relatives who lost ambulatory vision. DNA studies show linkage to the long arm of chromosome 22 and a point mutation in the tissue inhibitor of metalloproteinases-3 gene. Conclusion: This South African family presents with a dominantly inherited fundus dystrophy with clinical and molecular features compatible with Sorsby's fundus dystrophy.