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S. J. Bass, K. G. Noble, J. Sherman; Molecular Genetics Prove That Autosomal Dominant Pericentral Retinochoroidal Atrophy Is Really a Mild Form of Autosomal Dominant Retinitis Pigmentosa (adRP). Invest. Ophthalmol. Vis. Sci. 2007;48(13):3690.
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© ARVO (1962-2015); The Authors (2016-present)
To report the molecular genetics of a unique, newly described retinal disease previously called autosomal dominant pericentral retinochoroidal atrophy.
We reported a five-member pedigree having an unusual retinal disease characterized by annular or arcuate pericentral areas of retinochoroidal atrophy with normal visual acuity (ARVO 2003, Retina, 26:71-79, 2006). The inheritance pattern was autosomal dominant and this was the first pedigree to be reported. Absolute visual field loss was present in all affected individuals that corresponded to the areas of retinochoroidal atrophy. Younger members (4th decade) demonstrated retinal degeneration with corresponding angiographic hyperfluorescence and older members (7th decade) demonstrated retinochoroidal atrophy with corresponding angiographic hypofluorescence. Imaging studies (OCT and RTA ) revealed retinal thinning, even in the absence of ophthalmoscopic and angiographic evidence in some areas, and a normal retinal nerve fiber layer (GDxVCC). Although the absolute visual field loss and imaging studies were consistent with a photoreceptor degeneration, there was no nyctalopia, no arteriolar attenuation and no electrodiagnostic abnormalities except for the most severely affected individual. Blood samples were collected from the propositus, an asymptomatic 62 y-o white male with a normal ERG, and were commercially assayed for variations associated with adRP. Genomic DNA was isolated from the white blood cells and using an amplification refractory mutation system (ARMS), the DNA was initially assayed for pro23his, arg135trp and arg677stop, the most common RP-causing variants. Since there was no positive ARMS result, the entire coding regions of the RHO and RDS genes were amplified and screened for sequence variation using single-strand conformation polymorphism (SSCP) analysis.
A heterozygous ACG>ATG nucleotide substitution was detected on the RHO gene resulting in a Thr17Met amino acid change. This variation is consistent with a diagnosis of adRP. An estimate of pathogenic probability (EPP) was 3, indicating it to be a probable disease causing variation. Three additional variations were detected, but all had an EPP=0 (very unlikely to be disease-causing).
The molecular genetics of a previously described entity, initially called autosomal dominant pericentral retinochoroidal atrophy, indicate that this clinical condition is actually an unusual mild variant of adRP.
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