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A Ambresin, L El Matri, O Charfi, C Hamel, Y Arsenijevic, F-X Borruat, L Zografos, D Schorderet, F Munier; Genotype-Phenotype Correlation in Patients With a Severe Autosomal Recessive Retinal Degeneration Caused by an R91W Homozygous Mutation in the RPE65 Gene . Invest. Ophthalmol. Vis. Sci. 2002;43(13):793.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: 1) to identify the gene defect underlying autosomal recessive retinal degeneration in three consanguineous Tunisian families; 2) to correlate genotype to phenotype Methods: Three consanguineous families originating from the same village in the Tunisian Cap Bon were included in this study. All accessible family members had an ophthalmological examination including visual acuity, biomicroscopy, fundus exam and, when possible, fluorescein angiography and electroretinography (ERG) testing. A genome-wide screen was initiated, and mutation analysis was performed by bi-directional sequencing. Results: 11 out of 47 examined family members were affected with a severe form of retinal degeneration (age range:18-54 years). Blood sampling was obtained in 10 of them. Linkage analysis revealed a maximal lod score of 4.02 (θ=0.1) for the marker D1S207 on 1p31. Mutational screening of the RPE65 gene revealed an homozygous R91W (CGG to TGG) mutation (exon 4), co-segregating with the disease in all affected individuals. The clinical features included congenital nystagmus, nyctalopia and progressive loss of vision leading to light perception by the third decade of life. Biomicroscopy of the lens showed posterior polar cataracts in all patients and bilateral anterior polar cataracts in 2 patients. Fundoscopy revealed a waxy pallor of the disk and arterial narrowing of retinal vessels in all patients, with salt-and-pepper retinopathy by the second decade, associated with pigmentary and atrophic changes in older patients, consisting of mid-peripheral "leopard spots", and multifocal geographic atrophy of the retinal pigment epithelium-chorio-capillaris complex, best seen on fluorescein angiography. Scotopic ERG was non detectable by the fourth decade of life (n=7), while markedly reduced and delayed in the only teenager examined. Conclusion: We identified and characterized an endemic area of autosomal recessive retinal degeneration in a consanguineous population of North-Eastern Tunisia, due to the high prevalence of a single RPE65 mutation, most likely caused by a founder effect.
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