Novel phenotypic and genotypic findings in X-linked retinoschisis.
OBJECTIVE
To describe atypical phenotypes associated with the retinoschisis (X-linked, juvenile) 1 mutation (RS1).


METHODS
Seven patients with multiple fine white dots at the macula and reduced visual acuity were evaluated. Six patients underwent pattern and full-field electroretinography (ERG). On-off ERG, optical coherence tomography, and fundus autofluorescence imaging were performed in some patients. Mutational screening of RS1 was prompted by the ERG findings.


RESULTS
Fine white dots resembling drusenlike deposits and sometimes associated with retinal pigment epithelial abnormalities were present in the maculae. An electronegative bright-flash ERG configuration was present in all patients tested, and abnormal pattern ERG findings confirmed macular dysfunction. A parafoveal ring of high-density autofluorescence was present in 3 eyes; 1 patient showed high-density foci concordant with the white dots. Optical coherence tomography did not show foveal schisis in 3 of 4 eyes. All patients carried mutations in RS1, including 1 with a novel 206T-->C mutation in exon 4.


CONCLUSIONS
Multiple fine white dots at the macula may be the initial fundus feature in RS1 mutation. Electrophysiologic findings suggest dysfunction after phototransduction and enable focused mutational screening. Autofluorescence imaging results suggest early retinal pigment epithelium involvement; a parafoveal ring of high-density autofluorescence has not previously been described in this disorder.
Tsang
Stephen H
SH
Departments of Clinical Ophthalmology and Electrophysiology, Moorfields Eye Hospital, 162 City Road, London, England.
Vaclavik
Veronika
V
Bird
Alan C
AC
Robson
Anthony G
AG
Holder
Graham E
GE
D002648:Child; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005453:Fluorescence; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010857:Pigment Epithelium of Eye / Q000473:pathology; D016133:Polymerase Chain Reaction; D041441:Retinoschisis / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence
D005136:Eye Proteins; C108726:RS1 protein, human