Cone-rod dystrophy caused by a novel homozygous RPE65 mutation in Leber congenital amaurosis.
BACKGROUND
The aim of this study was to describe an unexpected phenotype in a family with Leber congenital amaurosis (LCA) due to a retinal pigment epithelium-specific protein 65 kDa (RPE65) homozygous mutation.


METHODS
We analyzed a family from Yemen in which 3 individuals were affected with LCA. Linkage analysis using markers flanking the known LCA genes was done, followed by direct sequencing of RPE65.


RESULTS
Severe visual impairment and night blindness were observed during infancy. We observed photophobia only in the 8-year-old patient. The youngest affected had bilateral hyperopia of +3.50 and visual acuity of 1/60. The oldest two had visual acuity limited to hand movements in the right eye (OD) and counting fingers in the left eye (OS) for the oldest and of 5/60 OD, 6/60 OS for the other. They showed disc pallor, attenuated vessels, white flecks in the retina mid-periphery and bull's eye maculopathy. ERGs of the oldest child were completely unresponsive. Genomic sequencing identified a novel homozygous missense mutation, IVS2-3C>G, in the second RPE65 intron.


CONCLUSIONS
We identified a novel LCA-related homozygous RPE65 mutation associated with a severe clinical presentation including an early and severe cone dysfunction. This is in contrast with the presentation associated with other RPE65 mutations predominantly causing rod-cone dystrophy with residual visual function.
IRO-Institute for Research in Ophthalmology, Sion, Switzerland.
C
C
Jakobsson
Department of Ophthalmology, Cairo University, Cairo, Egypt.
I S
IS
Othman
IRO-Institute for Research in Ophthalmology, Sion, Switzerland.
F L
FL
Munier
IRO-Institute for Research in Ophthalmology, Sion, Switzerland.
D F
DF
Schorderet
IRO-Institute for Research in Ophthalmology, Sion, Switzerland.
H
H
Abouzeid
D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000235:genetics*; D015006:Yemen; D019745:cis-trans-Isomerases / Q000235:genetics*; D000099178:Retinoid Isomerohydrolase
D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase