Correlation of ophthalmic examination with carrier status in females potentially harboring a severe Norrie disease gene mutation

Purpose: To correlate ophthalmic findings with carrier status for a severe Norrie disease (ND) gene mutation (C95F). Design: Prospective interventional case series. Participants: Six potential carriers and 1 obligate carrier from a family harboring the mutation. Methods: An ophthalmologist blind to the pedigree performed a full ophthalmic examination for the 7 asymptomatic family members. A peripheral blood sample was collected from each for ND gene sequencing. Main Outcome Measures: Ophthalmic examination findings (with attention to the presence or absence of retinal findings) and results of ND gene sequencing. Results: Three carriers were identified by molecular genetics, and all 3 of them had peripheral retinal abnormality. However, 3 of the 4 genetically identified noncarriers also exhibited peripheral retinal abnormality. Two of these noncarriers; with retinal findings were the offspring of a confirmed noncarrier. The genetically identified noncarrier with a normal peripheral retinal examination was the daughter of an obligate carrier. Conclusions: The presence of peripheral retinal changes was not useful for carrier prediction in a family harboring ND. There are likely additional loci responsible for phenotypic expression.