Helicoid subretinal fibrosis associated with a novel recessive NR2E3 mutation p.S44X.

Objectives: To describe a unique pattern of helicoid subretinal fibrosis associated with a novel recessive NR2E3 mutation and to highlight how examination of the proband's affected relative allowed appropriate genetic testing.
Design: Interventional family study (ophthalmic examination and candidate gene testing).
Results: The proband (mother), who complained of poor vision since early childhood, had bilateral helicoid subretinal fibrosis mostly involving the macula. Two children were symptomatic; one had ophthalmic findings similar to her mother while the second had macular retinoschisis, retinal pigment epithelium changes, and refractive accommodative esotropia. The father and third child were asymptomatic and had unremarkable ophthalmic examination findings. Based on the findings in the second symptomatic child, NR2E3 analysis was performed, which revealed homozygosity for a novel mutation, p.S44X, in all 3 affected individuals and heterozygosity for the mutation in both asymptomatic individuals.
Conclusion: Helicoid subretinal fibrosis is another potential phenotypic manifestation of recessive NR2E3 mutation.
Clinical Relevance: Examination of affected relatives can be helpful in guiding molecular genetic testing for hereditary eye disease when the proband's diagnosis is unclear.