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104. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft 2006
Abstract
Abstract
FR.14.10 Phenotype variability within members of a family carrying a novel mutation in the CRX gene Jägle H., Kitiratschky V., Zabel T., Zrenner E., Wissinger B., Kohl S.
University Eye Hospital Tübingen Objective: Progressive autosomal dominant cone and cone-rod dystrophies are a genetically and clinically heterogenic group of retinal dystrophies. To date mutations have been found in the RDS, GUCA1A, GUCY2D and CRX genes. Here we describe the variability of the phenotype within four members of a family carrying a novel mutation in the CRX gene.
Methods: DNA of family members of an affected individual was analysed by a mutation specific PCR/RFLP assay. Available patients underwent a detailed ophthalmologic examination and electrophysiological testing including visual acuity, color vision, visual field testing, dark adaptation, ISCEV Ganzfeld and multifocal ERG.
Results: A novel frame-shift mutation in exon 4 of the CRX gene, c.636delC, leading to a premature stop codon predicted to cause a truncation of the CRX polypeptide was found. Mutation analysis in the family confirmed segregation of the mutation with the disease phenotype, but also identified additional mutation carriers. Detailed clinical phenotyping of four available family members revealed that all tested mutation carriers showed clinical signs of cone dystrophy. Visual acuity was 0.1/0.1 (OD/OS) and 0.03/0.03 at the age of 45 and 47 years, and 0.8/0.8 and 1.0/1.0 at the age of 21 and 16 years, respectively. While visual field testing in all patients revealed a variable degree of sensitivity reduction only one patient showed peripheral visual field defects. ISCEV Ganzfeld ERG showed low rod and abnormal cone responses, the multifocal ERG showed pronounced central reduction in response amplitude and prolongation of the implicit time.
Conclusions: We identified a novel disease causing mutation in the CRX gene and described the variability of the corresponding phenotype. This emphasises the importance of detailed phenotype analysis in patients with known mutations to help to develop models of disease mechanism.
This study was supported by grants from the German Research Council (DFG): KFO134, Ko2176/1-1 donated to SK & BW and JA997/8-1 donated to HJ & EZ.
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