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M. Michaelides, G. E. Holder, A. G. Robson, A. T. Moore, A. J. Hardcastle; Detailed Phenotyping of an X-Linked Cone Dystrophy Pedigree and Exclusion of the CORDX1 Locus. Invest. Ophthalmol. Vis. Sci. 2008;49(13):6092. doi: https://doi.org/.
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To characterise the phenotype of an X-linked retinal dystrophy identified in a three-generation British family and to determine the underlying molecular genetic basis.
Five affected individuals and two obligate carrier females underwent ophthalmological examination, colour vision testing, colour fundus photography, autofluorescence imaging, and electrophysiological assessment. Two unaffected subjects also underwent clinical assessment. DNA was extracted for mutation screening of RPGR and haplotype analysis.
Affected subjects complained of reduced central vision starting in the first decade, with subsequent gradual deterioration of visual acuity and colour vision. All patients were myopic. A range of macular appearances were seen, varying from mild retinal pigment epithelial (RPE) changes to extensive macular atrophy. All five affected subjects had abnormal pattern ERGs consistent with macular dysfunction. All five also had evidence of generalised retinal dysfunction, with the cone system markedly more affected than the rod. S-cone ERGs were undetectable in two of the three affected subjects who were tested. Both obligate carriers had mild bilateral macular RPE changes and on electrophysiological assessment there was evidence of both bilateral macular and generalised cone dysfunction.Direct sequencing of RPGR failed to identify any disease-causing mutations. Haplotype analysis excludes CORDX1 (caused by mutations in RPGR ORF15), RP2 and CACNA1F as disease loci in this family.
We have identified a three-generation British family with X-linked cone-rod dystrophy. Known X-linked retinal degeneration genes on the short arm (Xp) have been excluded in this family by sequence and haplotype analysis. Extensive haplotype and linkage analysis is underway to determine the critical disease interval in this family.
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