The spectrum of retinal diseases caused by NR2E3 mutations in Israeli and Palestinian patients.
OBJECTIVE
To evaluate the involvement of NR2E3 in inherited retinal degenerative diseases in the Israeli and Palestinian populations and to study phenotypic variability in patients who are homozygous for the same mutation.


METHODS
Patients from 35 families underwent clinical evaluation, including a full ophthalmologic examination and electroretinography. Genetic analyses included direct sequencing of polymerase chain reaction products and haplotype reconstruction.


RESULTS
We recruited 6 consanguineous Muslim families and 2 Jewish families with enhanced S-cone syndrome. Patients from 4 of the Muslim families were homozygous for the same NR2E3 mutation, c.119-2A>C, but showed considerable variability in fundus appearance and retinal function, even among patients of comparable ages. Both Jewish patients were compound heterozygotes for the c.932G>A mutation in combination with c.194-202del9bp or a novel splice-site mutation, c.747+1G>C. Homozygosity analysis in 27 consanguineous families with retinitis pigmentosa revealed a homozygous mutation, c.932G>A, in 2 families. The electroretinographic responses in these patients were compatible with retinitis pigmentosa and did not show the characteristic enhanced S-cone syndrome pattern.


CONCLUSIONS
Our results demonstrate the involvement of NR2E3 in enhanced S-cone syndrome and retinitis pigmentosa phenotypes in our populations.


CONCLUSIONS
Patients with NR2E3 mutations may manifest variable phenotypes. Moreover, patients who are homozygous for the same NR2E3 mutation have variable expression of retinal disease, suggesting the involvement of modifier genes.
Bandah
Dikla
D
Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Merin
Saul
S
Ashhab
Munther
M
Banin
Eyal
E
Sharon
Dror
D
D000293:Adolescent; D000328:Adult; D018912:Arabs / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007514:Islam; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D008297:Male; D009154:Mutation; D057093:Orphan Nuclear Receptors; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014157:Transcription Factors / Q000235:genetics*; D014792:Visual Acuity
D005136:Eye Proteins; C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors