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


METHODS
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.


CONCLUSIONS
Helicoid subretinal fibrosis is another potential phenotypic manifestation of recessive NR2E3 mutation.


CONCLUSIONS
Examination of affected relatives can be helpful in guiding molecular genetic testing for hereditary eye disease when the proband's diagnosis is unclear.
Khan
Arif O
AO
Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, PO Box 7191, Riyadh 11462, Saudi Arabia. arif.khan@mssm.edu
Aldahmesh
Mohammed A
MA
Al-Harthi
Essam
E
Alkuraya
Fowzan S
FS
D000328:Adult; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004948:Esotropia / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005355:Fibrosis / Q000235:genetics; D005451:Fluorescein Angiography; D005808:Genes, Recessive; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012160:Retina / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000473:pathology; D041441:Retinoschisis / Q000235:genetics; D041623:Tomography, Optical Coherence
D005136:Eye Proteins; C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors