Screening Genes of the Retinoid Metabolism: NovelLRATMutation in Leber Congenital Amaurosis

Purpose To evaluate the mutation prevalence and phenotype in genes involved in the ocular retinoid metabolism. Design We analyzedLRAT, encoding the lecithin retinol acyltransferase, andRDH10, a retinal pigment epithelium-specific retinol dehydrogenase. Methods We screened by denaturing-high performance liquid chromatography (D-HPLC) and direct sequencing all coding exons ofLRATandRDH10in 216 patients, including 134 with simplex or multiplex retinitis pigmentosa and 82 with various types of flecked retinal dystrophies. Results Only nonpathogenic variants were found in this series. In an additional 2.5-year-old patient presenting with an "RPE65" phenotype (night blindness, photoattractivity, and visual improvement several months after birth), we discovered a homozygous deletion inLRAT(c.217_218delAT) leading to a premature stop at codon 120. Conclusions The phenotype of patients with mutations inLRATis similar to that of patients with mutations inRPE65, suggesting the need to systematically screen both genes in case of typical phenotype.