Purchase this article with an account.
S.M. Adams, R.G. Weleber, E.L. Berson, T.P. Dryja; A Screen for Mutations of the Aipl1 Gene in Patients With Supernormal Scotopic Erg B–Wave . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1820.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: The aryl hydrocarbon receptor–interacting protein–like 1 (AIPL1) is expressed specifically in adult rod photoreceptors where it is essential for photoreceptor viability and is one of the disease genes known to cause Leber congenital amaurosis. Mice homozygous with an AIPL1 hypomorphic mutation have a single flash rod response with a higher amplitude and a greater time–to–peak than wild–type mice (Liu X et al. Proc Nat Acad Sci 2004;101:13903–8). We hypothesized that a hypomorphic mutation in this gene might be associated with a similar retinopathy in humans. To test this hypothesis, we screened the AIPL1 gene for mutations in patients with a supernormal scotopic ERG b–wave (Sandberg MA et al. Invest Ophthal Vis Sci 1990;31:2283–7). Methods: Leukocyte DNA samples from 8 unrelated patients with good acuity, low rod responses to dim light and supernormal rod+cone responses to bright white light flashes were evaluated for mutations in all 6 coding exons and the flanking intron sequences by direct genomic sequencing. We also evaluated the DNA of relatives in 4 of the 8 probands. In total, 20 patients were screened. Results: One nonpathogenic missense change was found in 5 probands, Asp90His (GAC to CAC). This missense variant was found not to cosegregate with disease in one family. Three isocoding sequence substitutions were also found, Cys89Cys (TGC to TGT), Leu100Leu (CTA to CTG), and Pro217Pro (CCG to CCA). The missense change and the isocoding changes have been previously reported by other groups. Other variants identified were intronic, IVS1+36C>T, IVS1+45T>C, IVS2–10C>A, IVS4+48A>G, and IVS4–33T>C; which were all previously reported SNP’s (http://www.ncbi.nlm.nih.gov/). All sequence variants were evaluated with splice–site prediction software and were predicted not to alter RNA splicing. Conclusions: We found no evidence for AIPL1 mutations as a cause of retinopathy in patients with supernormal scotopic ERGs.
This PDF is available to Subscribers Only