Purchase this article with an account.
M.O. Sweeney, T.L. McGee, E.L. Berson, T.P. Dryja; Screen for Mutations the Lecithin Retinol Acyltransferase (LRAT) Gene in Patients With Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1685.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Lecithin retinol acyltransferase (LRAT) is an enzyme in the retinal pigment epithelium that catalyzes the esterification of all–trans–retinol. To our knowledge, only two isolate cases of recessive retinitis pigmentosa have been reported with biallelic LRAT mutations (Thompson et al. Nature Genet. 28, 123–124, 2001). We sought to find additional examples of patients with LRAT mutations.
We included 79 unrelated patients with Leber congenital amaurosis and 190 unrelated patients with recessive retinitis pigmentosa in this study. PCR conditions have been established to amplify each of the 3 exons of the LRAT gene along with their flanking intron DNA. The exon 3 amplicon included the entire coding sequence in that exon as well as 129 bp of 3’ untranslated region. The amplicons were amplified from leukocyte DNA samples from the patients and directly sequenced to search for mutations.
All 79 patients with Leber congenital amaurosis have been fully screened and 2 sequence changes were found in 3 patients. Two patients were heterozygotes for an isocoding change affecting codon Glu114 (GAG to GAA; c.555G>A). In the retinitis pigmentosa patients, analysis of 61% of the amplicons have been completed, and 2 sequence changes were found. One retinitis pigmentosa patient was a heterozygote with the isocoding Glu114 variant. Another retinitis pigmentosa patient was heterozygous for the missense change Thr88Pro (ACG to CCG; c.475A>C); this missense variant is unlikely to be pathogenic as this patient was found to have two mutations in the USH2A gene in a concurrent study.
To date, we have not found any patients with LRAT mutations. In view of our results and the paucity of cases reported in the literature, it is likely that LRAT mutations are a very rare cause of Leber congenital amaurosis or autosomal recessive retinitis pigmentosa.
This PDF is available to Subscribers Only