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104. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft 2006
Abstract
Abstract
FR.14.08 The end of uniformity  genetic and clinical heterogeneity in LCA patients Lorenz B., Paunescu K., Friedburg C., Preising M. N.
Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics, Klinikum University of Regensburg, Germany Objective: To compare the phenotype of various patients with childhood onset of clearly evident visual impairment due to a retinal dystrophy most frequently diagnosed as Leber Congenital Amaurosis (LCA).
Methods: Complete ophthalmological investigation including fundus photography, Ganzfeld-ERG, Goldmann kinetic perimetry, 2-colour threshold perimetry, fundus autofluorescence (AF) and OCT was carried out in 125 patients with childhood onset of clearly evident visual impairment due to a retinal dystrophy including severe and mild phenotypes. Screening for mutations was performed by Single Strand Conformation Polymorphism (SSCP) analysis and direct sequencing in GUCY2D, RPE65, AIPL1, CRB1, RPGRIP, LRAT, TULP1, and CRX.
Results: Mutations were identified in GUCY2D, RPE65, AIPL1, RPGRIP, and CRX. Each underlying gene was associated with a gene specific phenotype. GUCY2D expressed the most severe form with connatal manifestation of severe visual impairment but unremarkable fundus over many years. Variations in the expressivity of GUCY2D mutations could be shown depending on the position and kind of mutation i.e. in the catalytic or kinase domain, deletion or missense mutation. RPE65 could be identified by low but stable or even improving vision during the first decade and obvious lack of autofluorescence (AF) despite only moderate changes on funduscopy. Less frequently involved were mutations in AIPL1 and RPGRIP. AIPL1 mutations were associated with severe fundus changes classifiable as early manifesting retinitis pigmentosa causing almost complete loss of vision by the age of 2 years. RPGRIP did not produce a phenotype that helped to predict the underlying gene but this may be due to the limited number of patients identified in our set. CRX was not found in our set of LCA cases but in a few cases of progressive forms of cone rod dystrophy classifiable as such by 2-colour threshold perimetry. CRB1 mutations were not identified but have been published in cases presenting with preserved RPE near retinal vessels or with Coats-like changes of the retinal vasculature.
Conclusions: In a screen of 125 patients with childhood onset of clearly evident visual impairment due to a retinal dystrophy gene specific phenotypes could be identified allowing a prediction of the underlying gene. The prediction is more precise but also more divers the more patients have been identified for a specific gene.
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