Screening genes of the retinoid metabolism: novel LRAT mutation in leber congenital amaurosis.

PURPOSE: To evaluate the mutation prevalence and phenotype in genes involved in the ocular retinoid metabolism.

DESIGN

We analyzed LRAT, encoding the lecithin retinol acyltransferase, and RDH10, a retinal pigment epithelium-specific retinol dehydrogenase.

METHODS

We screened by denaturing-high performance liquid chromatography (D-HPLC) and direct sequencing all coding exons of LRAT and RDH10 in 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 in LRAT (c.217_218delAT) leading to a premature stop at codon 120.

CONCLUSIONS

The phenotype of patients with mutations in LRAT is similar to that of patients with mutations in RPE65, suggesting the need to systematically screen both genes in case of typical phenotype.