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Early-onset severe rod-cone dystrophy in young children with RPE65 mutations
B Lorenz1, P Gyürüs, M Preising
1Department of Pediatric Ophthalmology and Ophthalmogenetics, University of Regensburg, Germany. birgit.lorenz@klinik.uni-regensburg.de
Insights
Mutations in the RPE65 gene can cause early-onset severe rod-cone dystrophy, a form of Leber congenital amaurosis (LCA). Patients showed better visual function than typical LCA, with preserved peripheral vision and residual cone electroretinograms (ERGs).
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Leber congenital amaurosis (LCA) is a severe inherited retinal dystrophy.
- Mutations in the RPE65 gene are a known cause of LCA.
- Understanding the ocular phenotype associated with specific mutations is crucial for diagnosis and management.
Purpose of the Study:
- To characterize the ocular phenotype in infants and young children with RPE65 gene mutations.
- To correlate genotype with visual function and electroretinographic findings.
- To identify clinical features that suggest RPE65 mutations in early-onset visual impairment.
Main Methods:
- Screening for RPE65 mutations in four children from three families with severe early-onset retinal dystrophy.
- Longitudinal assessment of visual function from infancy to age 10 using age-adapted methods.
- Clinical examinations and electroretinograms (ERGs) in patients and their parents.
Main Results:
- All patients were compound heterozygous for RPE65 mutations.
- Despite severe visual impairment and congenital nystagmus in some, visual acuity was measurable, and peripheral vision was preserved.
- Rod electroretinograms (ERGs) were non-recordable, while cone ERGs were detectable; funduscopic changes included macular and peripheral granularity.
Conclusions:
- RPE65 mutations can lead to early-onset severe rod-cone dystrophy, presenting a specific form of LCA.
- Patients with RPE65 mutations may exhibit better visual function than typically seen in LCA, particularly compared to retGC1-associated cases.
- Suspect RPE65 mutations in infants with apparent blindness in dim light, light responsiveness, non-recordable rod ERGs, and residual cone ERGs.
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+5G-->A). 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.