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B. Lorenz, N. Hausotter-Will, C. F. Friedburg, F. Rüschendorf, M. N. Preising; RD3 Mutation in a Consanguineous LCA Family. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1655.
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© ARVO (1962-2015); The Authors (2016-present)
To identify the underlying gene defect in a consanguineous Kurdish LCA family with several affecteds.
Linkage analysis was performed in a consanguineous 4 generation Kurdish family with 5 affected children consistent with autosomal recessive inheritance. The patients were clinically examined by BCVA, Goldman visual field, Ganzfeld ERG, VEP, and funduscopy.RETGC1, RPE65, LRAT, AIPL1, CRX, CRB1 and CEP290 were submitted to mutation analysis by SSCP. Linkage analysis was performed by a SNP-microarray (Affymetrix Mapping 50k Xba 240 Array) assay.To limit the candidate region additional microsatellite markers were selected from the NCBI- dbSNP-Database according to the SNPs linked in the microarray assay. The microsatellite markers were amplified by standard PCR conditions. PCR products were analyzed on a QIAxcel capillary gel electrophoresis (Qiagen, Hilden). Alleles were determined from the electropherogramm and haplotypes were built in Cyrillic 2.1. RD3 was amplified by PCR in two amplicons and sequenced directly.
The patients presented with nystagmus, increased glare sensitivity, reduced BCVA since birth and progressive visual field constriction. VEP or ERG were below threshold in early childhood. Funduscopy at age 2 revealed constricted retinal vessels, pigment irregularities were seen in the periphery and the macula.Classical LCA genes were excluded. The SNP microarray assay was used to map the underlying gene defect to chromosome 1q31.3 - 1q32.3 covering known genes for retinal degenerations including CRB1, USH2a, and RD3. Linkage analysis reduced the candidate region to 3 Mb covering 138 genes including 10 genes involved in eye or brain function. RD3 was chosen for candidate analysis since it had been reported once in a single Indian LCA family. Direct sequencing of RD3 revealed a homozygous stop mutation (p.Y60X (c.180C>A)) in exon 2.
We identified the second family showing a mutation in RD3. It is the first nonsense mutation detected in RD3. This makes RD3 a rare cause in LCA.
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