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1 From the Department of Pediatric Ophthalmology and Ophthalmogenetics, University of Regensburg, Germany; and the 2 Institute of Human Genetics, University Hospital Eppendorf, Hamburg, Germany.
PURPOSE. To describe the ocular phenotype of patients with RPE65 mutations in infancy and young childhood.
METHODS. Four children from three families with severe early-onset visual impairment related to electrophysiologically detectable retinal dystrophy were screened for mutations in the RPE65 gene. Visual function from infancy to the age of 10 years was assessed with age-adapted methods. Clinical examinations and electroretinograms (ERGs) were also performed on the six parents.
RESULTS. In all three families, patients were compound heterozygous for
mutations of the RPE65 gene (ins144T/IVS1+5G
A,
R91W/Y368H, 1114delA+T457N/IVS1+5GA). Visual acuity was measurable
in all patients at the age of 6 to 10 years, despite severe visual
impairment noted during infancy and congenital nystagmus in three of
the four patients. Photophobia was not a feature. Funduscopic changes
were discrete, the most prominent finding being increased granularity
in the macula and the periphery. Peripheral vision was well preserved,
measured by Goldmann perimetry. Rod ERGs were not recordable, whereas
cone ERGs were detectable in early childhood. All features taken
together suggest a specific form of Leber congenital amaurosis (LCA)
distinguishable on clinical grounds. ERGs were normal in five of the
six parents. One father had an ERG compatible with congenital
stationary night blindness unrelated to his heterozygous state for the
RPE65 mutation.
CONCLUSIONS. RPE65 mutations on both alleles may be associated with early-onset severe rod–cone dystrophy. Visual functions of the four patients were better than is usually seen in LCA, in particular in cases associated with retGC1 mutations. RPE65 mutations should be suspected in infants who appear to be blind in dim surroundings but react to objects in bright illumination and have nonrecordable rod ERGs and residual cone ERGs.
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