Mutations in CRB1 are associated with a range of recessively inherited retinal dystrophies, including LCA, childhood- and juvenile-onset rod-cone and cone-rod dystrophies. Although the phenotype is usually severe, in milder cases there is a window of opportunity for therapeutic intervention in early childhood.
PurposeTo investigate and describe in detail the demographics, functional and anatomic characteristics, and clinical course of Leber congenital amaurosis (LCA) associated with mutations in the CEP290 gene (LCA-CEP290) in a large cohort of adults and children.DesignRetrospective case series.ParticipantsPatients with mutations in CEP290 identified at a single UK referral center.MethodsReview of case notes and results of retinal imaging (color fundus photography, fundus autofluorescence [FAF] imaging, OCT), electrophysiologic assessment, and molecular genetic testing.Main Outcome MeasuresMolecular genetic testing, clinical findings including visual acuity and retinal imaging, and electrophysiologic assessment.ResultsForty patients with LCA-CEP290 were identified. The deep intronic mutation c.2991+1655 A>G was the most common disease-causing variant (23/40 patients) identified in the compound heterozygous state in 20 patients (50%) and homozygous in 2 patients (5%). Visual acuity (VA) varied from 6/9 to no perception of light, and only 2 of 12 patients with longitudinal VA data showed deterioration in VA in their better-seeing eye over time. A normal fundus was found at diagnosis in younger patients (mean age, 1.9 years), with older patients showing white flecks (mean age, 5.9 years) or pigmentary retinopathy (mean age, 21.7 years). Eleven of 12 patients (92%) with OCT imaging had preservation of foveal architecture. Ten of 12 patients (83%) with FAF imaging had a perifoveal hyperautofluorescent ring. Having 2 nonsense CEP290 mutations was associated with worse final VA and the presence of nonocular features.ConclusionsDetailed analysis of the clinical phenotype of LCA-CEP290 in a large cohort confirms that there is a window of opportunity in childhood for therapeutic intervention based on relative structural preservation in the central cone-rich retina in a significant proportion of patients, with the majority harboring the deep intronic variant potentially tractable to several planned gene editing approaches.
Awareness of the risk of blindness from smoking is low among teenagers, but fear of blindness may be more likely to motivate teenagers to stop smoking than fear of lung or heart disease. Teenagers should be made more aware of the ocular risks of cigarette smoking as a novel public health measure.
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