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.