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F. Testa, S. Rossi, P. E. Bianchi, E. Fazzi, M. Fossarello, C. Ziviello, A. Auricchio, E. Rinaldi, F. Simonelli, S. Banfi; Clinical Genetic Multicentric Study on Leber Congenital Amaurosis: New Insight on Diagnosis and Follow Up. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1655.
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To carry out a comprehensive mutations analysis of an Italian population of Leber congenital amaurosis (LCA) patients and to perform a genotype-phenotype analysis.
DNAs from 95 patients with LCA were analyzed using a microarray chip containing previously identified disease-associated sequence variants in eight LCA genes. Patients with mutations underwent a detailed ophthalmological evaluation including autofluorescence and OCT analysis.
Pathogenic mutations were identified in 28% of patients with LCA. Six novel sequence variants were identified. Mutations were most frequently found in RPE65 (8.3%), GUCY2D (6.3%) and CRB1 (5.8%). Since early childhood, patients with RPE65 or GUCY2D mutations show minimal retinal abnormalities. Patients with CRB1 mutations progress from minimal retinal abnormalities to a retinitis pigmentosa. Almost all those with RPE65 mutations display normal OCT macular tickness whereas patients with CRB1 mutations have a reduced retinal tickness with a coarsely-laminated retina. The autofluorescence analysis demostrated the presence of fundus autofluorescence in 36% of patients carring RPE65 and GUCY2D mutations. No fundus fluorescence was elicitable in CRB1 patients.
Microarray-based mutation detection allowed the identification of 28% of LCA sequence variants and the RPE65 gene was found to be involved at a highly significant frequency in the pathogenesis of LCA in the Italian population. The present study establishes a possible association between the OCT profile and the presence or absence of fundus autofluorescence in RPE65 subjects. RPE65 patients retain minimal visual capabilities in the childood and are characterized by a greater integrity of RPE, as shown by normal retinal tickness associated with partially preserved fundus autofluorescence. On the contrary, CRB1 patients seem to present a more rapid progression of the disease, and a compromised integrity of RPE as assessed by OCT and autofluorescence analyses.
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