Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy

The chromophore of the visual pigments, 11-cis retinal, is derived from vit amin A tall-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1), The first of these reactions i s catalyzed by lecithin retinol acyltransferase (LRAT): (ref. 2). We screen ed 267 retinal dystrophy patients for mutations in LRAT and identified dise ase-associated mutations (S175R and 396delAA) in three individuals with sev ere, early-onset disease. We showed that the S175R mutant has no acyltransf erase activity in transfected COS-7 cells. Our findings highlight the impor tance of genetic defects in vitamin A metabolism as causes of retinal dystr ophies and extend prospects for retinoid replacement therapy in this group of diseases.