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

Nat Genet. 2001 Jun;28(2):123-4. doi: 10.1038/88828.


The chromophore of the visual pigments, 11-cis retinal, is derived from vitamin A (all-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1). The first of these reactions is catalyzed by lecithin retinol acyltransferase (LRAT); (ref. 2). We screened 267 retinal dystrophy patients for mutations in LRAT and identified disease-associated mutations (S175R and 396delAA) in three individuals with severe, early-onset disease. We showed that the S175R mutant has no acyltransferase activity in transfected COS-7 cells. Our findings highlight the importance of genetic defects in vitamin A metabolism as causes of retinal dystrophies and extend prospects for retinoid replacement therapy in this group of diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases / genetics*
  • Acyltransferases / metabolism
  • Age of Onset
  • Animals
  • COS Cells
  • Cell Membrane / metabolism
  • Female
  • Genes, Recessive
  • Humans
  • Male
  • Microsatellite Repeats
  • Mutation*
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • Retinal Degeneration / genetics*


  • Acyltransferases
  • lecithin-retinol acyltransferase